Relevant bibliographies by topics / Pre-Clinical tumor model

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  4. Conference papers

Academic literature on the topic 'Pre-Clinical tumor model'

Author: Grafiati
Published: 23 November 2024

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Journal articles on the topic "Pre-Clinical tumor model"

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Buxbaum, C., A. Deo, B. Manobla, S. Levin, S. Ash, and Y. Shaked. "P16.07.A STUDYING NEUROBLASTOMA TUMOR MICROENVIRONMENT THROUGH A NOVEL PRE-CLINICAL MODEL." Neuro-Oncology 26, Supplement_5 (October 2024): v85. http://dx.doi.org/10.1093/neuonc/noae144.282.

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Abstract BACKGROUND Neuroblastoma is a pediatric cancer that develops from neural crest cells. It has a dramatically variable course, ranging from very aggressive disease to benign differentiation and even spontaneous regression. In neuroblastoma, a crucial prognostic marker is the distinct cutoff at 18 months of age. Thus, children older than 18 months have a significantly worse prognosis than younger children. This age cutoff was studied thoroughly, but no explanatory mechanism has been found. All current pre-clinical research encompasses models in adult subjects while the development of tumors is greatly impacted by its microenvironment, which varies between young and adult individuals, thus creating disparate biological conditions. Therefore, the development of age-relevant neuroblastoma models is of great interest, especially when age is a major prognostic factor. MATERIAL AND METHODS C57BL/6 mice aged 12-days (young) and 8-weeks (adults) were used to reflect the different age groups, where 12-day-old mice correspond to children younger than 18-month. Mice were orthotopically implanted into the adrenal gland with 0.5 million 9464D-luciferase tagged murine neuroblastoma cells. Tumor growth assessment was performed once a week using micro-ultrasound to estimate tumor volume. At the endpoint, tumors were harvested and prepared for histopathological and immune characterization using flow and mass cytometry. RESULTS Tumors exhibited divergent growth patterns when comparing young and adult mice. In the initial week following implantation, tumors in young mice showed inhibited growth in contrast to those in adult mice (0.65mm3 vs. 5.44mm3 p=0.005). Following this initial phase, tumors in young mice started to grow rapidly, eventually leading to an equal final tumor load in both groups. The tumor characteristics were notably different between the groups. For example, the tumor immune cell infiltration exhibited a significantly increased number of B cells (3.598 vs. 10.01 p=0.01), CD4 cells (31.2 vs. 41.24 p=0.32) in young mice. Conversely, adults exhibited a higher number of G-MDS’c (32.2 vs. 13.856 p=0.005). CONCLUSION Our study reveals a delayed development of neuroblastoma in young mice during the early post-implantation phase. This observation mimics the natural biological behavior of this disease and potentially emulates the spontaneous regression seen in children under 18 months-old. In our investigation of the tumor microenvironment, we analyzed immune cell populations, revealing notable differences between the age groups. Further and updated findings are forthcoming. This study proposes a new approach for neuroblastoma research and potentially for all preclinical studies of pediatric cancer.
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Becker, William J., Purevdorj B. Olkhanud, and Jay A. Berzofsky. "Triple synergy between vaccine and checkpoint inhibitors in a pre-clinical tumor model." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 118.14. http://dx.doi.org/10.4049/jimmunol.208.supp.118.14.

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Abstract Despite advances in checkpoint inhibitor (CPI) therapy for cancer treatment, many malignancies remain resistant. Tumors deemed ‘cold’ based on lack of T cell infiltration into the stroma of the tumor show reduced potential for CPI therapy and finding the right combination to balance safety and efficacy is arduous. To study ways to circumvent these limitations, we used the preclinical mouse model of TC1 tumor cells resistant to conventional CPI therapy. The TC1 cells are transfected with oncogenes E6 and E7 of HPV16, and we designed a tumor-vaccine specific for an E7(43–77) peptide. We show the synergy between the tumor-antigen specific vaccine and the combination of two CPIs, anti-TIGIT and anti-PD-L1. The synergistic effect of the triple combination provides more protection against tumor growth than either treatment alone or any pairwise combination and significantly improves survival in a CD8+ T cell dependent manner. Combining the tumor-specific vaccine with CPIs induces tumor-specific CD8+ T cells that infiltrate the tumor in young and aged mice, although aged mice show less protection than their younger counterparts. These data show proof-of-concept for a novel combination of a vaccine designed to elicit de novo anti-tumor T cell responses that can be amplified by synergistic CPIs that lead to greater survival. Supported by Intramural NCI funding: ZIA-C-004020
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Ernst, Kati, Konstantin Okonechnikov, Laura von Soosten, Nina Hofmann, Norman Mack, Benjamin Schwalm, Robert J. Wechsler-Reya, et al. "BIOL-07. DISTINCTIVE FEATURES OF HIGH-GRADE GLIOMA MOUSE MODELS REVEALED BY SINGLE-NUCLEUS RNA-SEQUENCING GUIDE PRE-CLINICAL MODEL SELECTION." Neuro-Oncology 25, Supplement_1 (June 1, 2023): i7. http://dx.doi.org/10.1093/neuonc/noad073.026.

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Abstract Glioma is the most common pediatric central nervous system tumor, with high-grade gliomas (HGG) having one of the worst prognoses of all human cancers. In order to develop better diagnostics and therapies, it is essential to use faithful disease models. Currently, highly passaged patient-derived xenograft (PDX) models are most widely used in preclinical studies, although alternative immunocompetent models are becoming increasingly available. Here, we compare several in vivo glioma models on a single-cell level and investigate their similarity to primary human tumors. Single-nucleus sequencing was used to analyze >125,000 nuclei of primary patient samples, xenografts, autochthonous mouse tumors and related allografts including early and late in vivo passages – with a focus on MET-fusion-driven as well as H3 K27M-mutant HGG. Transcriptomic profiles of single tumor cells and associated stromal/immune components reveal insights into model-specific intratumoral heterogeneity, tumor evolution, and similarities between mouse models and patient samples. In addition, matched tumors engrafted into immunocompromised and immunocompetent animals are used to examine tumor-immune crosstalk and the modifying role of the tumor microenvironment. This improved understanding of how the analyzed model systems evolve over time and how they reflect patient’s tumor compositions will allow to prioritize and refine modern preclinical trials.
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Ahmed, Eman N., Lauren C. Cutmore, and John F. Marshall. "Syngeneic Mouse Models for Pre-Clinical Evaluation of CAR T Cells." Cancers 16, no. 18 (September 18, 2024): 3186. http://dx.doi.org/10.3390/cancers16183186.

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Chimeric antigen receptor (CAR) T cells have revolutionized the treatment of hematological malignancies. Unfortunately, this improvement has yet to be translated into the solid tumor field. Current immunodeficient models used in pre-clinical testing often overestimate the efficacy of CAR T cell therapy as they fail to recapitulate the immunosuppressive tumor microenvironment characteristic of solid tumors. As CAR T cell monotherapy is unlikely to be curative for many solid tumors, combination therapies must be investigated, for example, stromal remodeling agents and immunomodulators. The evaluation of these combination therapies requires a fully immunocompetent mouse model in order to recapitulate the interaction between the host’s immune system and the CAR T cells. This review will discuss the need for improved immunocompetent murine models for the pre-clinical evaluation of CAR T cells, the current use of such models and future directions.
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Klose, Johannes, Stefan Trefz, Tobias Wagner, Luca Steffen, Arsalie Preißendörfer Charrier, Praveen Radhakrishnan, Claudia Volz, et al. "Salinomycin: Anti-tumor activity in a pre-clinical colorectal cancer model." PLOS ONE 14, no. 2 (February 14, 2019): e0211916. http://dx.doi.org/10.1371/journal.pone.0211916.

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Weeber, Fleur, Salo N. Ooft, Krijn K. Dijkstra, and Emile E. Voest. "Tumor Organoids as a Pre-clinical Cancer Model for Drug Discovery." Cell Chemical Biology 24, no. 9 (September 2017): 1092–100. http://dx.doi.org/10.1016/j.chembiol.2017.06.012.

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Serritella, Anthony V., Pablo Saenz-Lopez Larrocha, Payal Dhar, Sizhe Liu, Milan M. Medd, Shengxian Jia, Qi Cao, and Jennifer D. Wu. "The Human Soluble NKG2D Ligand Differentially Impacts Tumorigenicity and Progression in Temporal and Model-Dependent Modes." Biomedicines 12, no. 1 (January 16, 2024): 196. http://dx.doi.org/10.3390/biomedicines12010196.

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NKG2D is an activating receptor expressed by all human NK cells and CD8 T cells. Harnessing the NKG2D/NKG2D ligand axis has emerged as a viable avenue for cancer immunotherapy. However, there is a long-standing controversy over whether soluble NKG2D ligands are immunosuppressive or immunostimulatory, originating from conflicting data generated from different scopes of pre-clinical investigations. Using multiple pre-clinical tumor models, we demonstrated that the impact of the most characterized human solid tumor-associated soluble NKG2D ligand, the soluble MHC I chain-related molecule (sMIC), on tumorigenesis depended on the tumor model being studied and whether the tumor cells possessed stemness-like properties. We demonstrated that the potential of tumor formation or establishment depended upon tumor cell stem-like properties irrespective of tumor cells secreting the soluble NKG2D ligand sMIC. Specifically, tumor formation was delayed or failed if sMIC-expressing tumor cells expressed low stem-cell markers; tumor formation was rapid if sMIC-expressing tumor cells expressed high stem-like cell markers. However, once tumors were formed, overexpression of sMIC unequivocally suppressed tumoral NK and CD8 T cell immunity and facilitated tumor growth. Our study distinguished the differential impacts of soluble NKG2D ligands in tumor formation and tumor progression, cleared the outstanding controversy over soluble NKG2D ligands in modulating tumor immunity, and re-enforced the viability of targeting soluble NKG2D ligands for cancer immunotherapy for established tumors.
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Breen, Kevin, Tuesday Haynes, Masashi Watanabe, and Mark Gilbert. "Abstract 2663: Determining the role of tumor mutational burden in a pre-clinical model of glioblastoma." Cancer Research 84, no. 6_Supplement (March 22, 2024): 2663. http://dx.doi.org/10.1158/1538-7445.am2024-2663.

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Abstract Despite advances in care in many cancer types, patients with glioblastoma (GBM) have a grim prognosis of 15 to 21 months and unchanged standard therapy since 2005. These tumors have a profoundly immunosuppressive tumor immune microenvironment. Immunotherapy, including the checkpoint inhibitors (ICIs) targeting PD-1 and CTLA-4, has transformed the treatment of many cancers but has failed in trials of both newly diagnosed and recurrent GBM. Tumor mutational burden (TMB) has been proposed as a predictor of response to ICI treatment, presumably through an increase in neoantigens that can be recognized by cytotoxic CD8+ T cells leading to tumor rejection. GBM typically has a low TMB, a feature speculated as a contributor to poor response to ICI treatment. However, cases with an extremely high TMB (i.e., patients with the biallelic mismatch repair deficiency syndrome) do show response to immunotherapy. To begin to investigate the impact of mutational burden on immune response in GBM, we created a murine syngeneic tumor model using CRISPR-Cas9 to knockout (KO) the mismatch repair protein Msh2, the lynchpin to mismatch recognition, in the SB28 GBM model that has a low TMB (108 mutations) at baseline. Msh2 KO increased the TMB from 2 to 12-fold depending on single cell sorted clone, resulting in between 150 and 200 predicted strong MHC-I binding neoantigens estimated by the NetMHC algorithm. Preliminary studies have demonstrated that in vitro proliferation is similar amongst low TMB and high TMB SB28 clones. Flank implantation of high TMB SB28 clones revealed slower growth compared to the low TMB SB28 tumors. Furthermore, treatment with ICIs did provide a survival advantage in this flank model. However, no survival advantage was noted when the high TMB clones were implanted intracranially either with or without ICI treatment. These results suggested that either there is poor immune cell trafficking to the intracranial tumors, or a robust immune response was causing increased intracranial pressure that is prematurely causing death. Use of dexamethasone starting at day 11 to control cerebral edema has shown some survival improvement with ICI treatment, supporting that an inflammatory response is at least partially responsible for the lack of improved survival in early studies. We are currently evaluating CD4+ and CD8+ T cell clonality, earlier timepoints to evaluate the immune infiltrate and anti-tumor immune response, and alterations in chemokines/cytokines in the tumor microenvironment. By creating high mutation burden clones from a GBM with a low mutational burden, we will be able to interrogate potential mechanisms of heightened immunogenicity that has been reported in other cancers. Citation Format: Kevin Breen, Tuesday Haynes, Masashi Watanabe, Mark Gilbert. Determining the role of tumor mutational burden in a pre-clinical model of glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2663.
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Longe, Harold O., Anupama Sinha, Douglas V. Faller, and Gerald V. Denis. "Telomere-Based Pre-Clinical Therapy of Human Lymphoid Malignancy in a SCID Xenograft Model." Blood 108, no. 11 (November 16, 2006): 4761. http://dx.doi.org/10.1182/blood.v108.11.4761.4761.

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Abstract We continue to develop and extend our novel adjuvant therapy approach to lymphoid malignancy. We supplement CHOP with DNA oligonucleotides that mimic the chromosomal telomere, which we call a “T oligo.” These agents are homologous to the 3′ overhang nucleotide sequence of telomeres and have previously been shown to have anti-tumor activity in animal models of malignant melanoma and breast cancer. They are currently being evaluated in melanoma and breast cancer patients. If introduced into human or murine normal, proliferating primary B cells or T cells, T oligo causes transient cell cycle arrest, while exerting no toxicity, but if introduced into human or murine malignant B cells or T cells, the arrest is followed by p53 phosphorylation, p21 message induction and ultimately p53-dependent apoptosis. Other p53-related effector molecules, such as p73, are also likely to be involved. The mechanism immediately suggests a novel method of chemotherapy for leukemia and lymphoma as an adjuvant with CHOP. Furthermore, we have previously shown with in vitro assay and in vivo mouse models of diffuse large B cell lymphoma (DLCL) that T oligo produces a more-than-additive toxicity towards lymphoma cells when combined with vincristine. T oligo alone or in combination with sub-therapeutic doses of CHOP, the standard of care for DLCL, dramatically reduced lymphoma burden in spleen, lung, bone marrow and peritoneum. In combination, which we refer to as T-CHOP, there was a greater reduction in tumor burden than with either therapy alone. We now show in SCID mouse xenograft models of human T cell malignancies, using a Jurkat T cell leukemic line or a MOLT-4 T cell leukemic line that T oligo also works alone to reduce tumor burden dramatically and increase survival. Interestingly, because T oligo-driven apoptosis occurs in p53-null, human lymphoid tumors, even chemotherapy-resistant lymphoid tumors are nevertheless sensitive to T oligo treatment, which may have profound benefit for relapsed leukemia or lymphoma patients.
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Ippagunta, Siri, Erik Emanus, Kelsey Bertrand, and Stephen Mack. "TRLS-16. RAPID GENERATION OF EPENDYMOMA MOUSE MODELS FOR PRE-CLINICAL STUDIES." Neuro-Oncology 25, Supplement_1 (June 1, 2023): i82. http://dx.doi.org/10.1093/neuonc/noad073.319.

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Abstract Pediatric Ependymomas are the leading cause of cancer death among children & adolescents with the 5-year progression free survival (PFS)rate being < 30%. Despite this poor prognosis there has been less success in development of targeted therapies. A major drawback in developing new therapeutics is lack of proper models of disease. Objective of out work has been to develop orthogonal models of various distinct groups of ependymoma to enable understanding of tumor microenvironment thus leading to strategies targeting potential therapeutic sites. In this regard we have developed two models of ZFTA-RELA Ependymoma: 1) In Utero Electroporation Model: DNA plasmids are transfected into developing forebrain, 2) Allograft Model: Primary tumor derived or in vitro transducer cells are allografted into various regions of brain. Further we have shown that these models molecularly resemble patient-derived tumors using RNA sequencing. Using these ZFTA-RELA mouse models we have shown that NSG mice (n=8/treatment group) treated with Selinexor (an XPO1 inhibitor) in combination with chemotherapy have lower tumor volumes by 40% as compared to vehicle or chemotherapy alone treated mice (P<0.05). Furthermore the combination therapy treated mice have improved survival by 28 days as compared to vehicle mice. In conclusion, we have shown that our novel models of ependymomas not only closely resemble disease in patients, but can also be used to develop effective targeted therapies.
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Dissertations / Theses on the topic "Pre-Clinical tumor model"

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Chen, Liu Qi. "Development and Application of AcidoCEST MRI for Evaluating Tumor Acidosis in Pre-Clinical Cancer Models." Diss., The University of Arizona, 2014. http://hdl.handle.net/10150/323450.

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Tumor acidosis is an important biomarker in cancer. We have developed a noninvasive imaging method, termed acidosis Chemical Exchange Saturation Transfer (acidoCEST) MRI to measure extracellular pH (pHe) in the tumor microenvironment. Chapter 1 introduces the importance of measuring tumor acidosis and presents various imaging modalities and their shortcoming to measure pHe. Chapter 2 describes the optimization of acidoCEST MRI for in vivo pHe measurement. The acidoCEST MRI protocol consists of a CEST-FISP acquisition and Lorentzian line shape fittings. We determined the optimal saturation time, saturation power and bandwidth, 5 sec, 2.8 µT and 90 Hz respectively. We also tried various routes of administration to increase contrast agent uptake in the tumor. We decided upon 200 µL bolus followed by 150 µL/hr infusion. The optimized acidoCEST MRI protocol was tested on a mammary carcinoma mouse model of MDA- MB-231. Our method can detect an increase in pHe in the bladder and tumor of the mice treated with bicarbonate. We used this optimized acidoCEST MRI method to measure pHe in lymphoma tumor model of Raji, Ramos and Granta 519 as described in Chapter 3. Pixel-wise pHe maps showed tumor heterogeneity. The pHe of Raji, Ramos and Granta 519 were determined to be mildly acidic with no significant difference. Chapter 4 describes the evolution of pixel-wise analysis in more detail. Besides the pHe map and spatial heterogeneity, we were able to determine the % contrast agent uptake. We monitored these biomarkers in two different mammary carcinoma mouse models, MDA- MB-231 and MCF-7 longitudinally and made comparisons between the different tumor models: MCF-7 were more acidic, more heterogeneous and faster growing than MDA- MB-231.
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Macedo, Gonzales Rodney. "Development of therapeutic vaccine strategies and pre-clinical animal tumor models for head and neck cancers." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066269/document.

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Les cancers des voies aéro-digestives supérieures, liés à la consommation d'alcool et de tabac mais également à l'HPV-16, ont un pronostic médiocre malgré les traitements actuels. Le développement de nouvelles stratégies innovantes dans des modèles précliniques adaptés est ainsi nécessaire. Nous avons préalablement développé une stratégie vaccinale ADN permettant l'auto-assemblage in vivo de pseudo-particules virales non infectieuses exprimant l'oncoprotéine E7 de l'HPV-16 (pVLP-E7). Nous avons notamment montré que l'injection de pVLP-E7 en intradermique (ID) était capable d'induire de bonnes réponses anti-tumorales dans un modèle murin de cancer obtenu en injectant dans le flanc des cellules d'une lignée exprimant les antigènes E6 et E7 de l'HPV-16, mais qu'il était nécessaire d'ajouter des adjuvants de types agoniste de TLR 7 et 9 dans des tumeurs avancées. Afin de tester de nouvelles voies vaccinales dans un modèle pertinent, nous avons développé un modèle orthotopique intrabuccal présentant des caractéristiques anatomiques et inflammatoires plus proches des cancers observés chez l'homme que le modèle ectopique. Dans ce modèle, nous avons testé une voie vaccinale muqueuse intrajugale qui a montré de meilleures réponses T CD8+ spécifiques en comparaison à la voie ID. Nous avons montré que ce type de vaccination en association à des adjuvants, était efficace dans des tumeurs établies, en lien avec une infiltration intratumorale et ganglionnaire de lymphocytes T CD8+ spécifique, permettant également une protection lors de rechallenge tumoral. Cette stratégie apparaît donc prometteuse dans le traitement de ces cancers fréquemment récidivants
Head and neck squamous cell cancer (HNSCC) associated with alcohol and tobacco consumption, and recently with human papillomavirus-16 (HPV-16), have bad prognosis despite current therapies. Development of innovative vaccine strategies and adequate pre-clinical tumor models are required to better evaluate HNSCCs. We developed a DNA vaccination that creates non-infectious virus-like particles, which express HPV-16 E7 oncoprotein (pVLP-E7). Results showed that pVLP-E7 induced an E7-specific immune response in vivo and in vitro. Moreover, using an ectopic model of HNSCC that expresses E6/E7 (TC-1), we found that pVLP-E7 intradermic (ID) immunizations induced anti-tumoral responses at early stages. For larger established tumors, pVLP-E7 vaccines were only efficient when administered with TLR-7 and TLR-9 agonists. In an orthotopic model that shares anatomical and inflammatory features with human HNSCC we observed that intra-cheek (IC) infusion of either TC-1 or NR-S1 cells into mice elicited higher numbers of inflammatory infiltrates in the tumor compared to ectopic models. Using this orthotopic IC model, we found that mucosal IC pVLP-E7 vaccination elicited better vaccine-specific CD8+ T-cell responses than ID administration in naive and tumor-bearing mice. Furthermore, pVLP-E7 IC immunizations in combination with TLR agonists led to rejection of established tumors and long-term protection, both of which were associated with E7-specific CD8+ T cell infiltration in tumors and lymph nodes. Our findings demonstrate that pVLP-E7 IC vaccination with adjuvants is efficient against these tumor models and together provides a valuable therapeutic strategy for HNSCCs
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Haagensen, Emma Joanne. "Pre-clinical evaluation of P13K and MEK inhibitor combinations in colorectal cancer tumour models." Thesis, University of Newcastle Upon Tyne, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.633014.

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Houel, Ana. "Étude de l’induction de structures lymphoïdes tertiaires, par virothérapie oncolytique, pour stimuler l’immunité antitumorale endogène." Electronic Thesis or Diss., Sorbonne université, 2024. http://www.theses.fr/2024SORUS232.

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Les structures lymphoïdes tertiaires (TLS) sont des agrégats organisés de cellules immunitaires qui se développent dans les tissus non-lymphoïdes à la suite d'une inflammation chronique. Les TLS matures, dont l'organisation est proche de celle d'un ganglion, sont associées à un bon pronostic dans les cancers à tumeurs solides et servent de prédicteur efficace de la réponse des patients traités par immunothérapie. Notre objectif a été d'étudier la virothérapie oncolytique comme stratégie pour induire des TLS dans le microenvironnement tumoral (TME) afin d'intensifier les réponses antitumorales.Les virus oncolytiques (OV) ont la capacité d'infecter et de se répliquer spécifiquement dans les cellules cancéreuses, induisant leur lyse directe ainsi que leur destruction par le système immunitaire via la mort immunogène. Nous supposons que la modulation du microenvironnement tumoral suite à l'infection par des OV, ainsi que la production locale de chimiokines exprimées par ces derniers, pourrait favoriser la néogenèse de TLS et amplifier les réponses antitumorales.Mes travaux ont alors consisté à générer et caractériser des virus de la vaccine oncolytiques (oVV) recombinants, armés avec trois chimiokines, CCL20, CCL21 et CXCL13, que nous supposons impliquées dans la néogenèse de TLS.J'ai observé que l'expression des chimiokines par les oVV recombinants n'affectait pas leurs propriétés oncolytiques et que les chimiokines étaient bien fonctionnelles in vitro. Bien que la réplication des oVV fût réduite dans les modèles murins syngéniques, j'ai détecté les chimiokines murines dans les tumeurs infectées avec les oVV armés ainsi que la formation d'agrégats immunitaires dans les modèles de tumeur chaude. Néanmoins, aucune amélioration thérapeutique n'a été observée avec l'oVV armé avec les chimiokines par rapport au virus non armé.J'ai alors étudié la capacité de TLS induites par un oVV, à établir des réponses antitumorales, dans le modèle orthotopique TC-1 luc qualifié de chaud. Dans ce modèle, j'ai observé que l'administration intranasale de l'oVV induisait plus de TLS que l'administration d'un virus de la vaccine non oncolytique, le MVA. De plus, j'ai observé que les TLS induites par l'infection virale par le MVA n'étaient pas associées à une réponse antitumorale alors que j'ai détecté à long terme la présence de lymphocytes T spécifiques antitumoraux et un contrôle de la tumeur pulmonaire chez une souris infectée par l'oVV. Ainsi, nous supposons que les propriétés oncolytiques des oVV peuvent induire des TLS efficaces contre les tumeurs.Pour favoriser la réplication des oVV et l'expression des chimiokines, ainsi que pour faciliter l'observation des réponses antitumorales tardives avec des cinétiques de croissance tumorale plus lentes, nous avons évalué l'efficacité d'une souche recombinante armée avec les trois chimiokines humaines (oVV-3hCK) dans un modèle de souris humanisées HIS-NXG greffées avec des tumeurs humaines.Dans ce modèle, les oVV (oVV-3hCK et oVV non armé) ont été particulièrement efficaces, ce qui n'a pas permis d'observer des différences d'efficacité thérapeutique entre les deux souches. Néanmoins, une augmentation significative de l'infiltration en cellules immunitaires CXCR5+ et en lymphocytes T et B naïfs a été observée dans les tumeurs infectées avec l'oVV-3hCK, confirmant l'activité chimiotactique des chimiokines et laissant supposer la présence de TLS dans les tumeurs.En conclusion, mes travaux de thèse ont confirmé que les trois chimiokines CCL20, CCL21 et CXCL13 exprimées par un oVV sont capables d'induire des agrégats immunitaires (ou TLS) dans le TME, et ont démontré la pertinence de cette stratégie pour améliorer la réponse antitumorale à long terme
Tertiary lymphoid structures (TLS) are organized aggregates of immune cells that develop in non-lymphoid tissues as a result of chronic inflammation. Mature TLS, which resemble lymph nodes in their organization, are associated with favorable prognoses in solid tumor cancers and serve as effective predictors of patient responses to immunotherapy. Our objective was to investigate oncolytic virotherapy as a strategy to induce TLS in the tumor microenvironment (TME) to enhance anti-tumor responses.Oncolytic viruses (OV) have the ability to specifically infect and replicate within cancer cells, inducing their direct lysis as well as their destruction by the immune system through immunogenic cell death. We hypothesize that the modulation of the TME following OV infection, along with the local production of chemokines expressed by these viruses, could promote TLS neogenesis and amplify anti-tumor responses.My work involved generating and characterizing recombinant oncolytic vaccinia viruses (oVV) armed with three chemokines, CCL20, CCL21, and CXCL13, which we hypothesize are involved in TLS neogenesis.I observed that the expression of chemokines by the recombinant oVVs did not affect their oncolytic properties and that the chemokines were functional in vitro. Although the replication of the oVVs was reduced in syngeneic murine models, I detected the murine chemokines in tumors infected with the armed oVVs and observed the formation of immune aggregates in hot tumor models. However, no therapeutic improvement was observed with the chemokine-armed oVV compared to the non-armed virus.I then studied the ability of TLS induced by an oVV to establish anti-tumor responses in the hot orthotopic TC-1 luc model. In this model, I observed that intranasal administration of the oVV induced more TLS than administration of a non-oncolytic vaccinia virus, MVA. Furthermore, I observed that TLS induced by MVA infection were not associated with an anti-tumor response, whereas I detected long-term presence of tumor-specific T lymphocytes and tumor control in the lungs of a mouse infected with oVV. Thus, we hypothesize that the oncolytic properties of oVVs can induce TLS that are effective against tumors.To promote oVV replication and chemokine expression, as well as to facilitate the observation of late anti-tumor responses with slower tumor growth kinetics, we evaluated the efficacy of a recombinant strain armed with the three human chemokines (oVV-3hCK) in a HIS-NXG humanized mouse model grafted with human tumors.In this model, the oVVs (oVV-3hCK and non-armed oVV) were particularly effective, making it difficult to observe differences in therapeutic efficacy between the two strains. Nonetheless, a significant increase in the infiltration of CXCR5+ immune cells and naïve T and B lymphocytes was observed in tumors infected with oVV-3hCK, confirming the chemotactic activity of the chemokines and suggesting the presence of TLS in the tumors.In conclusion, my thesis work confirmed that the three chemokines CCL20, CCL21, and CXCL13 expressed by an oVV are capable of inducing immune aggregates (or TLS) in the TME, and demonstrated the relevance of this strategy to improve long-term anti-tumor responses
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Baker, Amanda F., Neale T. Hanke, Barbara J. Sands, Liliana Carbajal, Janet L. Anderl, and Linda L. Garland. "Carfilzomib demonstrates broad anti-tumor activity in pre-clinical non-small cell and small cell lung cancer models." BioMed Central, 2014. http://hdl.handle.net/10150/610318.

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BACKGROUND: Carfilzomib (CFZ) is a proteasome inhibitor that selectively and irreversibly binds to its target and has been approved in the US for treatment of relapsed and refractory multiple myeloma. Phase 1B studies of CFZ reported signals of clinical activity in solid tumors, including small cell lung cancer (SCLC). The aim of this study was to investigate the activity of CFZ in lung cancer models. METHODS: A diverse panel of human lung cancer cell lines and a SHP77 small cell lung cancer xenograft model were used to investigate the anti-tumor activity of CFZ. RESULTS: CFZ treatment inhibited both the constitutive proteasome and the immunoproteasome in lung cancer cell lines. CFZ had marked anti-proliferative activity in A549, H1993, H520, H460, and H1299 non-small cell lung cancer (NSCLC) cell lines, with IC₅₀ values after 96 hour exposure from <1.0 nM to 36 nM. CFZ had more variable effects in the SHP77 and DMS114 SCLC cell lines, with IC₅₀ values at 96 hours from <1 nM to 203 nM. Western blot analysis of CFZ-treated H1993 and SHP77 cells showed cleavage of poly ADP ribose polymerase (PARP) and caspase-3, indicative of apoptosis, and induction of microtubule-associated protein-1 light chain-3B (LC3B), indicative of autophagy. In SHP77 flank xenograft tumors, CFZ monotherapy inhibited tumor growth and prolonged survival, while no additive or synergistic anti-tumor efficacy was observed for CFZ + cisplatin (CDDP). CONCLUSIONS: CFZ demonstrated anti-proliferative activity in lung cancer cell lines in vitro and resulted in a significant survival advantage in mice with SHP77 SCLC xenografts, supporting further pre-clinical and clinical investigations of CFZ in NSCLC and SCLC.
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Yeo, Syn Kok. "Investigating the therapeutic potential of targeting NF-kappaB p52 in pre-clinical models of breast cancer." Thesis, Cardiff University, 2012. http://orca.cf.ac.uk/26546/.

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Apoptosis is an important process in normal mammary gland physiology and has been implicated in mammary gland involution. In breast cancer cells, apoptotic resistance is an acquired feature that can promote tumour growth and progression. In order to assess the importance of apoptosis in these processes, caspases were directly inhibited by conditional expression of baculovirus p35 protein, a pan-caspase inhibitor, in the mammary glands of mice (rtTA/p35 mouse model). Inhibition of caspases during the first phase of involution in rtTA/p35 mice increased the number of sloughed luminal bodies which stained negatively for cleaved caspase-3. However, the total number of sloughed luminal bodies between mice with and without p35 expression was not changed. This suggests that caspase activation is not essential for the sloughing of mammary epithelial cells into lumen of alveoli and the initiation of involution may be a caspase-independent event. The importance of apoptotic resistance in breast cancer progression was also addressed by crossing rtTA/p35 mice with mice over-expressing the ErbB2 oncogene (Neu). Expression of p35 in established Neu mammary tumours did not affect the growth rates of tumours relative to un-induced controls. However, an increased number of mice with lung and liver metastases were observed when p35 was induced. This result substantiates the importance of apoptotic resistance in promoting metastasis and warrants the targeting of apoptosis regulators as an anti-metastatic therapy. The NF-κB signalling pathway regulates a range of anti-apoptotic genes and can also induce the expression of a variety of metastatic promoting genes. Accordingly, the role and potential of the NF-κB p52 subunit as a therapeutic target was investigated. Firstly, this was addressed by silencing the Nfkb2 gene, which encodes p100/p52, in mammary cancer cell lines. Interestingly, assessment of these cells in in vitro assays measuring motility and tumour initiating potential revealed opposing effects in differing cell lines upon Nfkb2 knockdown. In N202.1A cells (ER-ve/ErbB2+ve), therapeutically beneficial effects were seen whereas in the 4T1 cell line (ER+ve/ErbB2-ve), malignancy was exacerbated. One explanation for the differential effects observed is that the negative regulatory subunit p100 and the transcriptional subunit p52 alternately have dominant roles in the respective cell lines. Although these results demonstrate a role for p52 in regulating tumour initiating potential in particular cell lines, the contextual outcomes indicate that targeting p52 at the gene level may be detrimental in cases where the loss of p100 outweighs the loss of p52. This indicates that strategies aimed at disrupting p52 activity should circumvent the loss of p100. Therefore, we addressed the possibility of diminishing p52 transcriptional activity via promotion of repressive transcriptional complexes. As the formation of repressive complexes is favoured by phosphorylation of Ser-222 in p52, we addressed the effects of over-expressing the S222D p52 mutant in 4T1 cells. In in vitro assays assessing proliferation, colony forming potential, tumour initiating potential and motility, we did not observe any differences upon expression of S222D p52. However, over-expression of S222A p52 did increase the motility of 4T1 cells and this demonstrates that the lack of Ser-222 phosphorylation (promoting transcriptionally active complexes) can contribute to the malignancy of breast cancer cells. Due to the context dependent effects of Nfkb2 silencing, it was important to identify the particular subtypes of breast cancer which are dependent on p52 activity. We assessed a cohort of BRCA2-/- p53-/- tumours for nuclear p52 staining along with markers for respective breast cancer subtypes by immuno-histochemistry and found a positive correlation between p52 and p63. This suggests that aberrant p52 activity may be common in basal-like breast cancers which typically express p63 and could benefit most from p52 targeted therapies. In summary, our results indicate that targeting p52 in breast cancer cells can be therapeutically beneficial but only in particular subtypes of breast cancer and by certain therapeutic strategies.
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Valkenburg, Kenneth C. "Developing Pre-Clinical Mouse Models of Prostate Cancer| Deciphering the Roles of Tumor Suppressors Adenomatous Polyposis Coli and Smad4." Thesis, Van Andel Research Institute, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10274873.

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There are approximately 230,000 new diagnoses of prostate cancer every year in the U.S., making prostate cancer the most diagnosed cancer in men. It is responsible for approximately 30,000 deaths per year, with only lung cancer taking more lives. An important distinction must be made in men with prostate cancer. The majority of men with prostate cancer have a relatively indolent form of the disease, meaning high survival rates (100% survival 5 years after diagnosis) and no invasion of the tumor to other organs. However, approximately 4% of men are diagnosed with an aggressive form of the disease, and for these men, the survival rate is a mere 30% after 5 years. And for many patients, it is clinically difficult to differentiate between the indolent and the aggressive forms of the disease. Therefore, it is imperative to develop new genetic models of prostate cancer, and the mouse is an excellent model organism in which to do so. In 2009, mice were used to discover a new type of stem cell, called a castration-resistant Nkx3.1-?expressing cell in the luminal cell population of the prostate. We have used a mouse model targeting these cells to study the roles of two tumor suppressors, adenomatous polyposis coli (Apc) and Smad4. Apc down-regulates the Wnt signaling pathway, which is a carcinogenic pathway in the prostates of humans and mice. Deletion of Apc in mice causes an increase of Wnt signaling and prostate cells to proliferate but not invade, which represents a relatively indolent, precancerous phenotype. Smad4 is a transcription factor that controls the signaling of two pathways: transforming growth factor β and bone morphogenetic protein signaling. Deletion of Smad4 causes these pathways to shut off. When Apc and Smad4 are deleted simultaneously, mice develop aggressive, invasive prostate cancer. This work suggests that these two tumor suppressors – and the pathways they control – are important regulators of prostate cancer, could allow for clinicians to differentiate between indolent and aggressive disease, and should be targeted therapeutically in prostate cancer patients.

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Semenchenko, Kostyantyn. "Development of tumour therapies : from target validation of TTLL12 to tests of a small molecule XRP44X in pre-clinical models of cancer." Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAJ107.

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Les modifications post-traductionnelles de la tubuline sont des cibles attrayantes pour la thérapie du cancer. TTLL12 est impliqué dans la détyrosination de la tubuline, la triméthylation de l’histone H4K20 et le cancer de la prostate. La thèse porte sur les effets de la surexpression de TTLL12 sur ces modifications à différents stades du cycle cellulaire et sur la sensibilité à des agents ciblant les microtubules. Les résultats montrent que TTLL12 affecte ces modifications indépendant du cycle cellulaire et réduit la sensibilité des cellules à paclitaxel. XRP44X est un nouvel inhibiteur de la signalisation Ras-ERK-Elk3. Ses propriétés antitumorigène ont été montré in vitro et dans certaines études in vivo. Le projet de thèse était une continuation des études pré-cliniques sur XRP44X dans des modèles de cancer de la prostate de souris. Les résultats montrent que XRP44X est un inhibiteur efficace de la tumorigenèse et des métastases, ce qui peut être dû à son effet sur Elk3
Tubulin posttranslational modifications are an attractive target for cancer therapy. TTLL12 isinvolved in tubulin detyrosination, histone H4K20 trimethylation and prostate cancer. The thesis addresses the effects of TTLL12 overexpression on these tubulin and histone modifications at different stages of the cell cycle and on sensitivity to microtubule-targeting agents. The results show that TTLL12 over expression affects tubulin detyrosination and H4K20 trimethylation independently of cell cycle phase and reduces cell sensitivity totaxanes.XRP44X is a novel inhibitor of Ras-ERK1/2-Elk3 signalling and tubulin-binding agent. Itsantitumorigenic properties had been shown in vitro and in initial in vivo studies. The thesis project was a continuation of pre-clinical studies on XRP44X in mouse prostate cancer models. The results show that XRP44X is an effective inhibitor of tumorigenesis and metastasis in prostate cancer, which may be due to its effect on Elk3
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Rand, Taylor Ann. "Effect of head up tilt on tumor perfusion in a pre-clinical model of prostate cancer." Thesis, 2018. http://hdl.handle.net/2097/39407.

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Master of Science
Department of Kinesiology
Brad J. Behnke
Introduction: Prostate tumor arterioles lack functional smooth muscle and have a diminished myogenic response. Previous research has demonstrated an enhanced prostate tumor blood flow and oxygenation associated with the augmented mean arterial pressure during exercise. Thus, we tested the hypothesis that elevations in the heart-to-prostate tumor hydrostatic gradient via adoption of the 70˚ head-up tilt (HUT) body position would enhance perfusion of the prostate tumor, which may improve tumor oxygenation and radiation therapy outcomes (Study I). Based upon those findings, we performed a secondary analysis (Study II) on previously published prostate hemodynamic responses to an identical tilt-test between young and aged animals. Methods: Study I: Dunning Cell AT-1 tumor cells (100,000) were injected into the ventral lobe of the prostate in male Copenhagen rats (4 mo.; n = 7). Four to six weeks after injection blood flow to the prostate tumor, kidneys, and soleus muscle was measured via the fluorescent microsphere technique in the supine and HUT position. Study II: A secondary analysis was performed on blood flow to the prostate (host tissue of the tumor) in young (6 mo.; n =9) and aged (24 mo.; n=7) male Fisher 344 rats from Ramsey et al., 2007 (39) to determine potential age-associated differences in conductance to this tissue. Results: Study I: No significant difference was observed in blood pressure between the two body positions. Compared to the supine posture, there was a significant reduction in blood flow to the soleus muscle. There was no difference in prostate tumor blood flow or vascular conductance between the supine and HUT position. Study II: In response to tilt, there was a significant reduction in prostate vascular conductance in young rats versus that in the supine posture (P<0.05). In the aged animals, there was no difference in prostate vascular conductance with tilt. Discussion: Contrary to our hypothesis, we did not see any significant differences in either blood flow or vascular conductance to the prostate tumor with manipulations in body position. Importantly, we believe this may be an age-associated effect. Given tumors both co-opt existing arterioles from the host tissue that retain vasomotor control and develop new vessels that lack functional smooth muscle, the enhanced vascular resistance in the prostate with young animals during tilt likely contributed to the lack of change in tumor perfusion with body position given the rats from study I were also young. Given the lack of change in vascular conductance in the prostate with tilt in aged animals, future studies should be performed in aged models of prostate cancer, of which currently there are no immunocompetent aged rodent models of prostate cancer.
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Veloso, Susana Caçador. "Development of 3D cancer cell models for pre-clinical research : evaluation of the tumour microenvironment in 3D stirred-systems." Master's thesis, 2014. http://hdl.handle.net/10316/28094.

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Dissertação de mestrado em Biotecnologia Farmacêutica, apresentada à Faculdade de Farmácia da Universidade de Coimbra
Lung cancer is the leading cause of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) is the most frequent type of lung cancer, constituting approximately 85% off all lung cancer cases. Despite intensive research for the development of anti-NSCLC drugs, the majority fail in clinical trials. The reasons could be due to absence of therapeutic action and/or due to side effects, which could not be predicted in vitro or in animal studies because they lack the human physiological characteristics. Therefore, it is urgent to develop strategies to eliminate ineffective and unsafe compounds with speed, reliability and respect for animal welfare prior to clinical stages. Preclinical models that can better recapitulate tumour microenvironment features, such as the presence of different cell types (tumour and stromal cells) and extracellular matrix (ECM) components and their 3-dimensional (3D) spatial cellular organization, including cell-cell and cell-ECM interactions, would in principle predict clinical responses with higher accuracy. Tumour stroma is a supportive tissue around the tumour, with fibroblasts being the major cell population. Tumour-stroma crosstalk promotes changes in cancer cells and tumour microenvironment, enabling tumour progression, invasion and metastasis. 3D human cellular models overcome limitations of monolayer drug tests, such as the lack of cell-cell and cell-ECM interactions and 3D spatial cellular organization, better resembling physiological complexity and drug response than 2-dimensional (2D) culture. This allows a wide range of applications in pharmacological studies and in tumour biology since tumour microenvironment can be recapitulated with co-cultures of different type of cells and components, such as the stroma. The aim of this work was to develop scalable and reproducible 3D NSCLC human cellular models that could represent some of the above mentioned features. A 3D culture strategy was followed based on stirred culture systems. In a first approach, aggregation of NSCLC cell lines was implemented in spinner vessels. H460 and H1650 cell lines, representing large cell and bronchioalveolar carcinoma, respectively, formed cellular aggregates in suspension after 3 days of cell culture with high cell viability, cell proliferation and metabolic activity. In a second approach, 3D cell culture in stirred culture systems was combined with an alginate microencapsulation strategy for cell entrapment. H1650 cellular aggregates were encapsulated with and without immortalized normal lung fibroblasts as stromal component (mono and co-cultures, respectively). This strategy enabled to generate homogeneous microcapsules containing tumour cellular aggregates surrounded by fibroblasts, a configuration which resembles the in vivo situation. Moreover, this strategy XII enables collagen accumulation, characteristic of tumour microenvironment, such as ECM proteins production. Microcapsule cultures were maintained in stirred culture systems for 15 days, with high cell viability within aggregates. Cell proliferation and metabolism was similar in mono and co-cultures. Therefore, a 3D human NSCLC cellular model was accomplished, suggesting that the combination of 3D cell cultures, stirred culture systems and microencapsulation technique is a promising tool for the generation of more reliable NSCLC models that better mimic the tumour microenvironment and the possibility to study its influence in tumour progression
O cancro do pulmão é a maior causa de morte por cancro no mundo inteiro. O cancro do pulmão de não-pequenas células (CPNPC) é o tipo de cancro do pulmão mais frequente, constituindo aproximadamente 85% de todos os casos de carcinoma pulmonar. Apesar da investigação intensa para desenvolver fármacos contra este tipo de cancro, a maioria deles não ultrapassa a fase de ensaios clínicos. As razões podem ser devidas à ausência de efeito terapêutico e/ou aos efeitos secundários, que não foram previstos em estudos in vitro nem em estudos animais, uma vez que estes não possuem as características fisiológicas do sistema humano. Deste modo, é urgente eliminar os compostos ineficazes e não seguros com a maior brevidade e eficácia, reduzindo igualmente a experimentação animal. Os modelos celulares humanos 3-dimensionais (3D) superam algumas das limitações dos testes de fármacos em monocamada de células, tais como a ausência de interações célula-célula e a organização celular espacial em 3D, o que melhor mimetiza a complexidade e resposta fisiológica a fármacos, comparando com culturas celulares em 2-dimensões (2D). Os modelos celulares em 3D têm uma vasta aplicação em estudos farmacológicos e na biologia tumoral, uma vez que o microambiente tumoral pode ser mimetizado com co-cultura de diferentes tipos celulares e componentes, como o estroma. O estroma tumoral é um tecido de suporte que existe à volta do tumor, sendo os fibroblastos a maior população celular. Interações tumor-estroma promovem alterações nas células cancerígenas e no microambiente tumoral, permitindo a progressão, invasão e metástases tumorais. O objetivo do trabalho foi desenvolver um modelo celular 3D humano de CPNPC reprodutível e com aplicação em maior escala, com as características 3D descritas anteriormente. Foi usada uma estratégia 3D de cultura celular, baseada em sistemas de cultura agitados. Numa primeira abordagem, agregação de linhas celulares de CPCNP foi implementada. As linhas celulares H460 e H1650, representando carcinomas de grandes células e bronquioalveolar, respectivamente, formaram agregados em suspensão após 3 dias de cultura celular com alta viabilidade e proliferação celular e actividade metabólica. Numa segunda abordagem, cultura celular em 3D em sistemas de cultura agitados foi combinada com uma estratégia de encapsulação em alginato, para confinar as células no mesmo espaço físico. Agregados celulares de H1650 foram encapsulados sem e com fibroblastos do pulmão imortalizados, constituindo o componente estromal (mono- e co-cultura, respectivamente). Esta técnica possibilitou gerar cápsulas com agregados no seu interior e fibroblastos individuais à volta desses agregados, o que se aproxima da situação in vivo. Microcápsulas XIV foram mantidas em sistemas de cultura agitados até 15 dias, com alta viabilidade celular nos agregados. Proliferação e atividade metabólica foi semelhante em mono- e co-cultura. Esta estratégia permite ainda acumulação de colagénio, característica do microambiente tumoral devido à produção de proteínas da matrix extracelular, Assim, foi possível obter um modelo celular 3D humano de CPNPC, o que sugere que a combinação de cultura celular 3D, sistemas de cultura agitados e microencapsulação é uma ferramenta promissora para alcançar modelos celulares mais eficazes que melhor mimetizam o microambiente tumoral e a possibilidade de estudar a sua influência na progressão do tumor
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Book chapters on the topic "Pre-Clinical tumor model"

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Audigier, Chloé, Tommaso Mansi, Hervé Delingette, Saikiran Rapaka, Tiziano Passerini, Viorel Mihalef, Raoul Pop, et al. "Challenges to Validate Multi-Physics Model of Liver Tumor Radiofrequency Ablation from Pre-clinical Data." In Computational Biomechanics for Medicine, 27–38. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-28329-6_3.

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Hou, H., N. Khan, and P. Kuppusamy. "Measurement of pO2 in a Pre-clinical Model of Rabbit Tumor Using OxyChip, a Paramagnetic Oxygen Sensor." In Advances in Experimental Medicine and Biology, 313–18. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-55231-6_41.

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Rossmeisl, John H., Paulo A. Garcia, John L. Robertson, and Rafael V. Davalos. "Irreversible Electroporation for the Treatment of Brain Tumors: Pre-clinical Results in a Canine Model of Spontaneous Glioma." In IFMBE Proceedings, 809–12. Cham: Springer International Publishing, 2015. http://dx.doi.org/10.1007/978-3-319-11128-5_201.

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Abou-el-Enein, Mohamed, and Jordan Gauthier. "The Value of CAR-T-cell Immunotherapy in Cancer." In The EBMT/EHA CAR-T Cell Handbook, 231–34. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-94353-0_46.

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AbstractThe development of genetically modified chimeric antigen receptor (CAR) T-cells to target cancer by conferring tumour antigen recognition has tremendously improved the fight against the disease and broadened treatment options for haematological malignancies (Elsallab et al. 2020b). However, in contrast to conventional drugs that patients can easily access, the implementation of CAR-T-cell therapy in routine clinical practice poses significant challenges. Access to CAR-T-cell products is currently limited to specific certified centres meeting the requirements set up by manufacturers and regulatory agencies. There are also issues regarding insurance coverage, reimbursement, affordability, and pricing, which have critical impacts on broadening patient access to these novel therapies (Abou-El-Enein et al. 2016a, b). Current list pricing ranges between $373,000 and $475,000 per one-time infusion for the four CAR-T-cell therapies currently approved by the FDA (tisagenlecleucel, Kymriah®; axicabtagene ciloleucel, Yescarta®; brexucabtagene autoleucel, Tecartus®; lisocabtagene maraleucel, Breyanzi®). In addition to the cost of the CAR-T-cell product, patient preparation (leukapheresis and/or lymphodepletion), product infusion, pre- and post-infusion patient management, and monitoring for side effects (Wagner et al. 2021) significantly add to the final price tag. There are calls for restructuring the current payment and reimbursement models to allow better access to CAR-T-cell therapies (Abou-El-Enein et al. 2014). However, this would only be possible after examining the strength of clinical evidence generated during product development (Abou-El-Enein and Hey 2019; Elsallab et al. 2020a) and, most importantly, by determining the value of CAR-T-cell therapy.
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Bellone, Matteo, Sara Martina Parigi, and Elena Jachetti. "Pre-clinical evaluation of immunotherapy: The case for prostate cancer and the TRAMP model." In Tumor Immunology and Immunotherapy, 173–88. Oxford University Press, 2014. http://dx.doi.org/10.1093/med/9780199676866.003.0012.

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Nguyen, Quynh T. N., Phuc T. Phan, Shwu-Jiuan Lin, Min-Huei Hsu, Yu-Chuan (Jack) Li, Jason C. Hsu, and Phung-Anh Nguyen. "Machine-Learning Based Risk Assessment for Cancer Therapy-Related Cardiac Adverse Events Among Breast Cancer Patients." In Studies in Health Technology and Informatics. IOS Press, 2024. http://dx.doi.org/10.3233/shti231116.

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The study aims to develop machine-learning models to predict cardiac adverse events in female breast cancer patients who receive adjuvant therapy. We selected breast cancer patients from a retrospective dataset of the Taipei Medical University Clinical Research Database and Taiwan Cancer Registry between January 2004 and December 2020. Patients were monitored at the date of prescribed chemo- and/or -target therapies until cardiac adverse events occurred during a year. Variables were used, including demographics, comorbidities, medications, and lab values. Logistics regression (LR) and artificial neural network (ANN) were used. The performance of the algorithms was measured by the area under the receiver operating characteristic curve (AUC). In total, 1321 patients (an equal 15039 visits) were included. The best performance of the artificial neural network (ANN) model was achieved with the AUC, precision, recall, and F1-score of 0.89, 0.14, 0.82, and 0.2, respectively. The most important features were a pre-existing cardiac disease, tumor size, estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), cancer stage, and age at index date. Further research is necessary to determine the feasibility of applying the algorithm in the clinical setting and explore whether this tool could improve care and outcomes.
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Jain, Ayushi, Neha Mittal, Madasu Hanmandlu, and Arvind Pandey. "Skin Lesion Detection." In Advances in Systems Analysis, Software Engineering, and High Performance Computing, 204–24. IGI Global, 2024. http://dx.doi.org/10.4018/979-8-3693-5643-2.ch008.

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In recent times, various imaging methods and deep learning models have been utilized for identification and analyzation of pigmented lesion images. Clinical and pathological methods of recognizing skin tumors are difficult, time consuming, painful, and expensive. In order to address this problem, many computers aided systems were developed and they achieved great success in detecting several lesions. Owing to the complex behavior of skin lesion images the identification of lesions is still challenging. The identification of skin cancer is making major advances by using the improved CAD models. This study presents an asystematic review of the advances made in each step of a CAD based on deep learning. These steps include pre-processing, segmenting, extracting features, classification, and the state of art approaches used in them. The existing models and the publicly available databases that involve both macroscopic and dermoscopic images are also discussed.
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Conference papers on the topic "Pre-Clinical tumor model"

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Smith, David J., Sean J. Josephson, and John C. Bischof. "A Model of Cryosurgical Destruction in AT-1 Prostate Tumor Based on Cellular Damage Mechanisms." In ASME 1997 International Mechanical Engineering Congress and Exposition, 149–50. American Society of Mechanical Engineers, 1997. http://dx.doi.org/10.1115/imece1997-1326.

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Abstract The thermal history during a prostate cryosurgery is known to lead to different cooling rates, end-temperatures and end-times within a cryosurgical iceball. The tissue exposed to this range of thermal histories will experience thermally-induced biophysical events which affect cell viability (dehydration and intracellular ice formation. IIF), injury due solely to the temperature and time of exposure, and injury due to host response. In this study, the dehydration and IIF behavior of single AT-1 prostate cancer cells is experimentally measured, the biophysical parameters of water transport and IIF are obtained, and the probability of injury to single AT-1 cells due to dehydration (Prd) and IIF (PIF) is predicted for a variety of cryosurgically-relevant thermal histories. In addition, viability data obtained after cooling to different end-temperatures at constant coolins rates is used to create an empirical function of injury for single AT-1 cells based solely on end-temperature (Pre). A total cellular injury model which then combines the biophysical mechanisms of injury as well as the empirically-obtained temperature viability function is created. This model is used to predict worst-case (i.e. highest possible survival) cryosurgical destruction in an AT-1 tumor; the implications for clinical cryosurgery are discussed.
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Leishman, Andrew, Olivia Harris, Jane Coates Ulrichsen, James Harper, Amy Popple, Marianna Papaspyridonos, Geoff Williams, et al. "Abstract 1651: Profiling immune cells within the tumor microenvironment for optimal model selection for pre-clinical investigations." In Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-1651.

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Turbitt, William J., Rachael M. Orlandella, Justin T. Gibson, and Lyse A. Norian. "Abstract 509: Acarbose, but not metformin, reduces tumor burden and improves intra-tumoral immune responses in a pre-clinical breast cancer model." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-509.

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Turbitt, William J., Rachael M. Orlandella, Justin T. Gibson, and Lyse A. Norian. "Abstract 509: Acarbose, but not metformin, reduces tumor burden and improves intra-tumoral immune responses in a pre-clinical breast cancer model." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.am2019-509.

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Paramathas, Sangeetha, Nathan Lewis, Tanya Guha, Zainab Motala, and David Malkin. "Abstract 2741: Assessing the utility of circulating tumor DNA as a surveillance tool for sarcomas and Li-Fraumeni syndrome using a pre-clinical model." In Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-2741.

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Krishnamoorthy, Murali, Rahul Pal, Hannah Collins, and Anand T. N. Kumar. "Fast fluorescence lifetime imaging system for intraoperative surgical guidance." In Clinical and Translational Biophotonics. Washington, D.C.: Optica Publishing Group, 2024. http://dx.doi.org/10.1364/translational.2024.tm5b.5.

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We present a novel fast fluorescence lifetime imaging (FLT) system for high-resolution real-time intraoperative guidance, showcasing surgeries in pre-clinical mouse tumor models and ex− vivo clinical specimens for contrast-enhanced tumor identification.
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Torres-Dominguez, Lino E., Lina S. Franco, Mario Abrantes, Benjamin S. Walker, Zachary Tacner, Cassandra Kien, Anna K. Waters, Grant McFadden, Steven J. Potts, and Leslie L. Sharp. "Abstract PR008: Armed Myxoma virus demonstrates therapeutic activity in pre-clinical xenograft models." In Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; October 19-20, 2020. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/2326-6074.tumimm20-pr008.

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Lau, Sai Ping S., Priscilla P. Kinderman, Melanie M. Lukkes, Floris F. Dammeijer, Heleen H. Vroman, Menno M. van Nimwegen, Thorbald T. van Hall, et al. "Abstract B117: Allogeneic tumor-lysate loaded dendritic cells induce anti-tumor immunity and tumor responses in pre-clinical models of pancreatic adenocarcinoma: Towards clinical trials." In Abstracts: Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; September 30 - October 3, 2018; New York, NY. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/2326-6074.cricimteatiaacr18-b117.

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Duarte, Antonio, Ana-Rita Pedrosa, Alexandre Trindade, Catarina Carvalho, José Graça, Sandra Carvalho, Maria C. Peleteiro, and Ralf H. Adams. "Abstract 5225: Endothelial-specific Jagged1 blockade prevents solid tumor growth in pre-clinical models." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-5225.

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Satyam, Leena Khare, Sanjita Sasmal, Manoj K. Pothuganti, Sreevidya M.R., Ashokk Ettam, Sireesha Nunna, Marla Roshaiah, et al. "Abstract 3844: Anti-tumor efficacy of SMARCA degraders in pre-clinical models of cancer." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.am2019-3844.

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