IndraLab
Statements
sparser
"Additionally, the CAM-PDX model versatility offers the ability to study other processes important to the development and progression of tumors (i.e. angiogenesis, invasion, metastasis, hypoxia, etc.) as well as the feasibility of employing longitudinal imaging and biosafety evaluation of promising compounds ( xref ; xref )."
sparser
"Freezing samples prior to engraftment also has the benefit of widening the availability of tissue, and therefore the appeal of the CAM-PDX model, to researchers who may be unable to readily obtain fresh tissue, for example due to a lack of local specialist hospitals or clinical collaborators."
sparser
"Due to the limitations of an mPDX model, alternative PDX and PDX-derived models were developed such as zebrafish patient-derived xenografts (zPDXs), chick chorioallantoic membrane patient-derived xenografts (CAM-PDXs), humanized mPDX, PDX-derived organoids (PDXO) and cell cultures (PDXC)."
sparser
"Published studies report high engraftment rates (70-80%), histological concordance with tumor type and a strong correlation between CAM-PDX assay results and patient outcome ( xref , xref , xref ), supporting the CAM model as an alternative method for generating physiologically applicable PDXs that can be utilized for drug screening and personalized medicine."
sparser
"Specific objectives of the presented work were (1) the establishment of a CAM-PDX model based on PDOs derived from a liver metastasis of a CRC patient and (2) the evaluation of the presented translational pipeline (patient – in vitro PDOs – in vivo CAM-PDX) regarding morphology, histopathology, expression of CXCR4, and radiotracer uptake patterns."
sparser
"Overall, these data show successful engraftment on the CAM following reanimation after freezing and it should be noted that despite the sparse tumor cell content of the example CAM-PDX shown in xref , it offers proof of principle of the methodology irrespective of how challenging the sample is."
sparser
"Therefore, we aimed to (1) establish a CAM patient-derived xenograft (PDX) model based on PDOs generated from the liver metastasis of a colorectal cancer (CRC) patient and (2) to evaluate the translational pipeline (patient – in vitro PDOs – in vivo CAM-PDX) regarding morphology, histopathology, expression of C-X-C chemokine receptor type 4 (CXCR4), and radiotracer uptake patterns."
sparser
"Since pleural mesothelioma is a heterogenous cancer, where tumor cell content and distribution can differ greatly between, and within patient samples ( xref ), a workflow to facilitate pre-screening of the tissue samples ( xref ) was employed to optimize selection for implanting and ensure regions with a greater proportion of tumor cells are prioritized for generating the CAM-PDXs."
sparser
"Therefore, PDX models are extensively exploited in clinical trials for the treatment of patients with metastatic renal cell carcinoma (CAM-PDX model, NCT04602702), recurrent metastatic head and neck squamous cell carcinoma (mPDX model, NCT02752932), metastatic prostate cancer (mPDX model, NCT03786848)."
sparser
"For example, the first step of drug screening should be carried out using high-throughput models such as cell cultures, spheroids, organoids, as well as PDX-derived cell cultures and organoids, the second step of screening should be based on high-throughput animal models such as zPDX and CAM-PDX, and finally, activity of the most promising candidates should be confirmed using an mPDX model."
sparser
"Re-culturing CAM-PDXs resulted in viable post-ovo PDO lines ( n = 3, Fig. xref B) exhibiting morphology and growth characteristics similar to the original PDO line (Fig. xref A). [ 68 Ga]Pentixafor was moderately taken up in both pre-ovo and post-ovo PDOs (Fig. xref C, Supplementary Table 1)."
sparser
"To visualize viable mesothelioma cells within the CAM-PDXs in ovo , we required an imaging modality that is suitable for unlabeled tissue and we therefore utilized [ 18 F]-FDG PET/CT. [ 18 F]-FDG is a non-metabolizable glucose analogue widely used as a radiotracer in oncology, including mesothelioma ( xref ), as elevated glucose uptake is commonly observed in cancer cells due to the Warburg effect ( xref )."
sparser
"This work reports the successful establishment of a CAM-PDX model derived from liver metastasis organoids from a CRC patient highly recapitulating the patient’s characteristics: The morphology, histopathology, and CXCR4 expression of the patient’s liver metastasis were reflected in in vitro PDOs and especially in CAM xenografts underlining the translational value of this alternative in vivo model for CRC patients."
sparser
"PET imaging after intravenous administration of [ 18 F]-FDG revealed tracer uptake ( xref ) in the CAM-PDX which were established from the same cryopreserved epithelioid tissue shown in xref - xref . [ 18 F]-FDG uptake indicates that the CAM-PDXs were sufficiently well vascularized to accumulate administered substances, such as the radiotracer, from circulating blood, and that they are metabolically active."
sparser
"Quantification of the PET signal, reported as total accumulated SUV across the entire CAM-PDX (SUVacc), showed similar uptake in CAM-PDXs (Two Sample t-test, p = 0.76), irrespective of the cryopreservation media used ( xref ), suggesting that both freezing methods preserve viable tissue that can be reanimated for engraftment."
sparser
"We optimized engraftment conditions for primary MIBC tumors using the CAM-PDX model and tested concordance between cisplatin-based chemotherapy response of patients to matching PDX tumors using tumor growth coupled with immunohistochemistry markers of proliferation and apoptosis."
sparser
"Albeit, ex vivo assessment of [ 68 Ga]Ga-Pentixafor uptake in CAM-PDXs did not reveal a significant difference between the baseline and blocking group (mean uptake 11.23 vs. 8.91%ID/g), possibly due to the low CXCR4 expression combined with a small amount of inoculated cells (1 × 10 5 PDOs) and a natural egg-to-egg variation."
sparser
"Further, proteogenomic informed kinase inhibitor use on MIBC CAM-PDX models suggests a benefit from integration of rapid in vivo testing of novel therapeutics to inform more complex, pre-clinical mouse PDX experiments for more effective clinical trial design aimed at achieving optimal precision medicine for patients with limited treatment options."
sparser
"Due to the immunodeficient nature of the chick embryo and the abundant vascularization of the CAM, this in vivo model has proven to be very useful for the implantation of various types of cancer cell lines and patient-derived tumor cells or explants. xref , xref The CAM-PDX model is well suited for rapid tumor engraftment and subsequent testing of therapeutic approaches."
sparser
"Kaplan-Meier analysis of PFS curves indicates that recurrence tends to occur later in patients with low tumor fragment uptake on CAM compared to those with a high uptake ( xref ), whereas a significant association was observed between CAM-PDX engraftment and overall patient survival ( xref )."
sparser
"To determine whether the CAM-PDX model can be used as an Avatar model to predict clinical responses in patients with glioma, we retrospectively evaluated treatment response in 15 HGG patients and their corresponding CAM-PDX models that were treated with optimized doses of TMZ, carboplatin, or vehicle alone."
sparser
"Treatments were considered effective in CAM when they resulted in a >30% and significant inhibition of tumor volume, according to the internationally standardized clinical Response Evaluation Criteria In Solid Tumors. xref These criteria were adapted to the CAM-PDX model by using the control group as a reference."
sparser
"Patient response was classified as either CR, PR, or SD, which are generally considered therapeutically beneficial in a clinical setting, or PD. xref summarizes the chemosensitivity profiles of these 14 glioma patients who generated 15 matched CAM-PDX models, 2 of which were derived from the same patient."
sparser
"This engraftment rate in the CAM-PDX model was higher than those observed in heterotopic mouse PDX glioma models, which ranged from 38% to 69%, xref , xref but more comparable to, yet higher than, the orthotopic model of brain tumors, which showed a 76%–90% success rate. xref , xref Of note, all 25 IDH-mutated samples successfully engrafted in the CAM model."
sparser
"In fact, this sample was identified as a giant cell glioblastoma, a rare variant of glioblastoma IDH -wild type characterized by frequent TP53 mutations, a marker associated with GBM subclonal heterogeneity. xref , xref These results highlight that, while CAM xenografts generally retain key features of the parental tumor, further studies will be needed to define whether this GBM variant should be included in an eventual glioma CAM-PDX precision medicine platform."
sparser
"Even though further evaluation of the correlation between patient responses and corresponding PDX in a larger prospective setting will be required, these data suggest that the glioma CAM-PDX model has a high potential to become a valuable platform for modeling clinical response in patients."
sparser
"The manuscript entitled " Methodology for generating chorioallantoic membrane patient-derived xenograft (CAM-PDX) models of pleural mesothelioma and performing preclinical imaging for the translation of cancer studies and drug screening" written by Schulze
and and his colleagues is a study that describes the procedure to generated a CAM-PDX from mesothelioma."