Podcasts about xenograft

"Never mind manoeuvres, always go at them". Dr. Bob Bloch from the University of Maryland School of Medicine joins us to discuss his development of the human FSHD muscle xenograft mouse model that is a key tool in the pre-clinical testing pipeline for FSHD therapeutics and biomarker discovery. --- Send in a voice message: https://anchor.fm/peter-l-jones/message

A new research paper was published in Oncotarget's Volume 13 on October 19, 2022, entitled, “Therapeutic efficacy of the humanized JAA-F11 anti-Thomsen-Friedenreich antibody constructs H2aL2a and H3L3 in human breast and lung cancer xenograft models.” The Thomsen-Friedenreich antigen (TF-Ag-α) is found on ~85% of human carcinomas but is cryptic on normal tissue. The humanized, highly specific hJAA-F11-H2aL2a and -H3L3 antibodies target TF-Ag-α without binding to TF-Ag-beta (found on surface glycolipids of some normal cells). “The relative affinity of H3L3 is 17 times that of H2aL2a, which would seem to favor superior efficacy, however, increased affinity can result in less tumor penetration.” In a new study, researchers Diala Ghazal, Fatma Zalzala, John C. Fisk, Swetha Tati, Loukia G. Karacosta, Susan Morey, James R. Olson, Sally Quataert, Grace K. Dy, and Kate Rittenhouse-Olson from For-Robin, Inc, University at Buffalo, University of Rochester, and Roswell Park Comprehensive Cancer Center Buffalo aimed to assess the potential therapeutic efficacy of these antibodies by treating four human cancer- mouse xenograft models with H2aL2a and H3L3. The tumor xenograft models used were human non-small cell lung cancer, H520, and small cell lung cancer, HTB171 in nude mice and human triple negative breast cancer, MDA-MB-231 and HCC1806 in SCID mice. H2aL2a significantly decreased tumor growth in both breast and both lung cancer models. H2aL2a showed statistically equal or better efficacy than H3L3 and has superior production capabilities. These results suggest that H2aL2a may be superior as a naked antibody, as an antibody drug conjugate or as a radiolabeled antibody, however the higher affinity of H3L3 may lead to better efficacy in bi-specific therapies in which the binding is decreased due to the presence of only one TF-Ag-α binding site. “In conclusion, both H2aL2a and H3L3 humanized antibodies to TF-Ag-α show efficacy in in vivo xenograft models of human tumors in SCID and nude mice and thus hold promise as therapeutics for breast and lung cancer. H2aL2a significantly decreased tumor growth rate in both breast cancer and both lung cancer models tested. H2aL2a is equal to or better than H3L3 in four of the four models and H2aL2a cell lines have far superior antibody production capabilities under the conditions tested.” DOI: https://doi.org/10.18632/oncotarget.28282 Correspondence to: Kate Rittenhouse-Olson - krolson@buffalo.edu Keywords: hJAA-F11, TF-Ag, Thomsen-Friedenreich antigen, tumor immunotherapy, translational oncology About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter - https://twitter.com/Oncotarget Facebook - https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram - https://www.instagram.com/oncotargetjrnl/ LinkedIn - https://www.linkedin.com/company/oncotarget/ Pinterest - https://www.pinterest.com/oncotarget/ LabTube - https://www.labtube.tv/channel/MTY5OA SoundCloud - https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com. Oncotarget Journal Office 6666 East Quaker Str., Suite 1A Orchard Park, NY 14127 Phone: 1-800-922-0957 (option 2)

Many people are waiting for an organ donation and some of them may die before a suitable organ is found. Some researchers think that in the near future we will be able to grow organs in animals to be safely transplanted into humans. This healthcare potential raises ethical questions and we need to assess where we stand on such technological change. The first of two features about medicine's use of animals for organ and tissue transplantation. This program was originally broadcast in October 2021.

This podcast is part of the 2017 NSH Symposium/Convention Poster Podcast Series.  The lead author of this poster is Anna Hughes. For more information on the author and to view the abstract, visit The Block.

Dr. Nathan Pennell, Cleveland Clinic, evaluates chemotherapy sensitivity assays, describing the difficulties inherent in predicting response to chemotherapy agents.

Dr. Nathan Pennell, Cleveland Clinic, evaluates chemotherapy sensitivity assays, describing the difficulties inherent in predicting response to chemotherapy agents.

Dr. Nathan Pennell, Cleveland Clinic, evaluates chemotherapy sensitivity assays, describing the difficulties inherent in predicting response to chemotherapy agents.

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumour in adults with a median survival, despite of multimodal aggressive therapy, of only 15 months. Relapse occurs inevitably because of the infiltrative nature of GBM. To date, only the MGMT promoter methylation is a reliable marker for therapy sensitivity. Survival-associated prognostic factors as well as novel therapy targets are urgently needed. Multiple genetic and metabolic pathway alterations contribute to tumour progression and therapy resistance. Recently proposed CSC markers for solid cancers include the aldehyde dehydrogenase (ALDH) superfamily. This cytoplasmic enzyme family consists of 19 different isoforms. The ALDH enzymes act upon oxidative stress and participate in proliferation, differentiation, and cell cycle arrest. The evolutionary conservation of the protein family enables comparative considerations of different species. In the presented study, isotype specific expression of ALDH is analysed in human GBM tumours and in two commonly used mouse GBM models. Expression of ALDH in the mouse models is then compared with the human GBM to find a suitable model for further research. The presented results indicate that there is, though challenging, a necessity for isotype specific analysis of ALDH expression. ALDH1A1 immunohistochemical expression in human PGBM was found primarily in the tumour adjacent region, whereas ALDH1A3 positive cells were more frequently found among tumour cells. Prognostic relevance for PGBM patients’ outcome was found for the ALDH1 immunohistochemical expression. Moreover, female PGBM patients were shown to have prolonged survival if neither ALDH1A1 nor ALDH1A3 expression is present. For male PGBM patients, ALDH1A1 and ALDH1A3 immunohistochemical expression could not be correlated to the medium overall survival. The reasons for this gender difference remain yet undetermined. Both the murine and the human GBM cells analysed in this thesis did not show ALDH1A1 immunohistochemical expression in cell culture or after implantation. The expression of ALDH1A3 is inhomogeneous in the analysed groups, raising further questions, which will be investigated in the future.The investigative approach of this thesis showed that the analysed canine GBM samples express ALDH1A3 but not ALDH1A1. This difference to human PGBM tumours in ALDH expression can help to understand more about the metabolic processes in tumour cells and the reactions to the tumour cells in the surrounding tissue. Finally, there are two particularly promising research subjects for future investigations: the gender specific prognostic power of ALDH expression in PGBM patients and the reason for the change in ALDH1A3 expression between in vitro and in vivo conditions. This knowledge can contribute to finding new targets for PGBM therapy and to prolonging patient survival.

Maurizio Scaltriti explains why a combination therapy that targets the PI3K-Akt pathway and signaling through the growth factor receptors EGFR and HER3 may be effective against triple-negative breast cancer.

Xenograft mouse models represent helpful tools for preclinical studies on human tumors. For modeling the complexity of the human disease, primary tumor cells are by far superior to established cell lines. As qualified exemplary model, patients' acute lymphoblastic leukemia cells reliably engraft in mice inducing orthotopic disseminated leukemia closely resembling the disease in men. Unfortunately, disease monitoring of acute lymphoblastic leukemia in mice is hampered by lack of a suitable readout parameter.

Background: Erufosine is a promising anticancer drug that increases the efficacy of radiotherapy in glioblastoma cell lines in vitro. Moreover, treatment of nude mice with repeated intraperitoneal or subcutaneous injections of Erufosine is well tolerated and yields drug concentrations in the brain tissue that are higher than the concentrations required for cytotoxic drug effects on glioblastoma cell lines in vitro. Methods: In the present study we aimed to evaluate the effects of a combined treatment with radiotherapy and Erufosine on growth and local control of T98G subcutaneous glioblastoma xenograft-tumours in NMRI nu/nu mice. Results: We show that repeated intraperitoneal injections of Erufosine resulted in a significant drug accumulation in T98G xenograft tumours on NMRI nu/nu mice. Moreover, short-term treatment with 5 intraperitoneal Erufosine injections caused a transient decrease in the growth of T98G tumours without radiotherapy. Furthermore, an increased radiation-induced growth delay of T98G xenograft tumours was observed when fractionated irradiation was combined with short-term Erufosine-treatment. However, no beneficial drug effects on fractionated radiotherapy in terms of local tumour control were observed. Conclusions: We conclude that short-term treatment with Erufosine is not sufficient to significantly improve local control in combination with radiotherapy in T98G glioblastoma xenograft tumours. Further studies are needed to evaluate efficacy of extended drug treatment schedules.

Tue, 21 Jul 2009 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/12570/ https://edoc.ub.uni-muenchen.de/12570/1/Thoenes_Lilja.pdf Thoenes, Lilja ddc:540, ddc:500, Faku

The human colon cancer cellline HT29 was investigated in various models regarding different criteria. The in-vivo-experiments were carried out with female SCID mice and consisted of subcutaneous cell injection, orthotopic cell injection into the cecal wall and orthotopic fixation of a tumor fragment onto the cecum. The subcutaneous experiment took 41 days; the orthotopic animal experiments were equally divided into three points of necropsy each two weeks apart. On these days tumor, liver and lung were withdrawn, fixed in 3,8% formaldehyde and analyzed histologically. In addition blood samples of all animals of the orthotopic experiments were taken on days of autopsy and the CEA (carcinoembryonic antigen) content was determined using an ELISA. The vascularization of the orthotopic primary tumors was examined by staining of CD34, i.e. number and area of the tagged vessels were ascertained. Additionally the green fluorescent protein (GFP) was studied in view of its suitability as quantifiable reporter gene in these models. Therefore not only HT29-wildtype but also HT29 cells transfected with GFP were used in vitro and in the first two in vivo assays. Advantages and disadvantages summarized: - The subcutaneous model was realized easily, measurement of the primary tumor was simple, the tumor take rate was 100 % and the laboratory animals appeared to suffer only from a relative slight amount of stress. Besides these advantages this setting cannot be used for investigations regarding metastasis because of the low number of metastases. - The orthotopic cell injection generated small, hardly measurable primary tumors, but this approach is a suitable model of metastasis because of the number of metastases detected. The technical effort and the burden for the animals exceeded that found in the subcutaneous setting but was below the effort of orthotopic fixation of a tumor fragment. - Of all investigated models the orthotopic fixation of a tumor fragment represents the model with the greatest effort. The primary tumors were big enough to be measured, but the number of metastases was too low to make statistical valuable evaluations. - The CD34 staining successfully marked the vessels of the primary tumor and facilitated a computer-assisted quantitative analysis of the vascularization of orthotopic colon tumors. It was assessed that a broad neoangiogenesis occurred at the beginning of tumor growth prior to the development of metastases. The number of metastases increased with proceeding length of time, whereas the number of vessels decreased. The continuous extension in tumor volume resulted in a necrotic tumor center so that vessels were detectable in the border area only. - The used HT29-GFP clone was not stable enough to generate sufficient fluorescence. The cells both in vitro an in vivo grew more slowly, the subcutaneous tumors showed necrotic areas and there were less metastases after orthotopic injection of GFP cells than after injection of wildtype cells. Because of the insufficient fluorescence it was not possible to execute a quantifiable analysis of metastasis. The application of GFP was not advantageous within these models. - CEA suits to be a valuable tumor marker for colon cancer in both investigated models. The CEA content in the blood samples of tumor bearing animals increased dependent on tumor burden and tumor invasiveness. A direct correlation between tumor size and CEA might be established with an improved measurement system or rather an advanced measuring of tumor volume. Due to the comparative characterization of injection and implantation techniques as well as other detailed examinations carried out for this thesis, it is possible to select suitable models for preclinical trials depending on the individual purpose.

Fri, 29 Nov 2002 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/656/ https://edoc.ub.uni-muenchen.de/656/1/Schneider_Tanja.pdf Schneider, Tanja ddc:570, ddc:5