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At least 19 recordsLinked to original sources

PubMed1975

[Experimental xenografting in widely divergent species: Interaction of humoral factors in hyperacute xenograft rejection in the rat-dog system (author's transl)].

The purpose of this paper is to test serum factors which are by interaction with cells responsible for the HXAR. Special stress was laid upon the examination of different serum fractions with or without the presence of preformed natural antibodies. Xenohemoperfusion: Rat kidneys were isolated and perfused in vitro with both whole blood resp. serum fractions and various perpheral cells of dogs. Rejection criterion was the diminishing renal blood flow at a constant pressure of the perfusion. Perfusate: Dog serum fractions were isolated by means of carton electrophoresis into the following fractions: Albumin, alpha-1, alpha-2, beta and gamma-globulin. Dog peripheral blood cells were separated into WBC, RBC and platelets by means of centrifugation and washing of EDTA whole blood. The serum fractions were tested for antibodies using hemagglutination and complement fixation techniques. 1. Hemoperfusion with serum fractions leads to a longer perfusion rate and to higher renal blood flow than perfusion with whole dog blood. 2. No preformed natural antibodies were found in the alpha-2 globulin fractions; however, perfusion with alpha-2 globulin fractions produced a rejection phenomenon both in combination with cells and erythrocytes. 3. Perfusion with serum fractions containing preformed natural antibodies produced a rejection only when WBC and thrombocytes were present. These results suggest that HXAR is induced by two different mechanisms: 1. The effect of humoral natural antibodies (found in the beta and gamma globulin fraction) together with peripheral cells. 2. The effect of a non-immunological humoral factor, found in the alpha-2 globulin fraction, leading to destruction of the xenogeneic organ, obviously to a minor degree dependent on interaction with peripheral cells.

Alpha-Globulins↗

PubMed2021

Presence of complete murine viral genome sequences in patient-derived xenografts.

Patient-derived xenografts are crucial for drug development but their use is challenged by issues such as murine viral infection. We evaluate the scope of viral infection and its impact on patient-derived xenografts by taking an unbiased data-driven approach to analyze unmapped RNA-Seq reads from 184 experiments. We find and experimentally validate the extensive presence of murine viral sequence reads covering entire viral genomes in patient-derived xenografts. The existence of viral sequences inside tumor cells is further confirmed by single cell sequencing data. Extensive chimeric reads containing both viral and human sequences are also observed. Furthermore, we find significantly changed expression levels of many cancer-, immune-, and drug metabolism-related genes in samples with high virus load. Our analyses indicate a need to carefully evaluate the impact of viral infection on patient-derived xenografts for drug development. They also point to a need for attention to quality control of patient-derived xenograft experiments.

Animals↗

PubMed1977

Long-term experience with porcine aortic valve xenografts.

Between 1971 and 1975, glutaraldehyde-preserved porcine aortic valve xenografts were employed for isolated replacement of the mitral valve (MVR) in 243 patients, replacement of the aortic valve (AVR) in 167 patients, and double valve replacement (AVR and MVR) in 51 patients. Postoperatively, long-term anticoagulation was not routinely given. Operative mortality rates for AVR, MVR, and double valve groups were 7.8, 6.0, and 11.8 per cent, respectively; the majority of early postoperative deaths were associated with concomitant coronary artery disease. No death was attributable to xenograft dysfunction. Follow-up of all patients was obtained. The total duration of follow-up for the MVR group was 347 patient-years, for the AVR GROUP 148 148 patient-years, and for double valve replacement 37 patient-years; maximum follow-up for these three groups was 4.4, 4.0, and 2.4 years, respectively. Actuarial analysis of postoperative survival rates at a common interval of 3 years showed 78 per cent for MVR patients, 91 per cent for AVR patients, and 80 per cent (projected) for patients with double valve replacement (85, 96, and 91 per cent for operative survivors, respectively. At this same interval 92 per cent of MVR patients, 99 per cent of AVR patients, and 93 per cent (projected) of patients with double valve replacement were free of thromboembolic episodes. Altogether, 12 of the total 512 valves implanted exhibited some evidence of dysfunction during the entire period of follow-up evaluation, but in only 2 instances (both mitral) was intrinsic pathological involvement of the xenograft tissue documented. Actuarial analysis of xenograft dysfunction at a common interval of 3 years after operation showed 95 per cent of MVR patients, 98 per cent of AVR patients, and 97 per cent (projected) of patients with double valve replacement to be free of this complication. These data support the use of glutaraldehyde-preserved porcine xenografts as superior bioprostheses that pose a low risk of thromboembolism without anticoagulation. The over-all durability of such valves, within the restriction of a maximum current follow-up interval of 4.4 years, appears comparable to that of currently available mechanical prostheses and justifies continued clinical use.

Animals↗

PubMed2026

Standardized Xenograft Models for Preclinical Cancer Research.

Xenograft models are the principal in vivo platform of preclinical oncology and the most established experimental link between cell culture and clinical investigation. From the carcinogen-exposed rabbit models of the early twentieth century through the current generation of humanized patient-derived xenograft (PDX) systems, these platforms have evolved in response to the demands of translational cancer research. This review critically examines the biological principles, methodological standards, and translational applications of the principal xenograft platforms in current use. Cell line-derived xenograft (CDX) models remain the most widely used and most cost-effective modality for preclinical efficacy testing, offering the reproducibility, scalability, and accessibility that have sustained their role across oncology drug development pipelines for decades. PDX models have emerged as the preferred platform for co-clinical trial design, predictive biomarker discovery, and personalized oncology applications, preserving the genomic landscape, intratumor heterogeneity, and histological architecture of the donor tumor across serial passages. The engraftment biology of PDX systems, including immunodeficient host strain selection, implantation site, tumor source, and passage biology, is reviewed, together with humanized and autologous humanized configurations that extend the platform to immune checkpoint inhibitors, bispecific T-cell engagers, and chimeric antigen receptor T (CAR-T) cell therapy evaluation. This review addresses preclinical-to-clinical translation as a function of immunological divergence, incomplete tumor microenvironment recapitulation, and standardization. Formal frameworks, including the PDX Model Minimal Information (PDX-MI) standard and the Minimal Information for Standardization of Humanized Mice (MISHUM), are examined alongside global biobank infrastructure and emerging AI-driven translational modeling approaches.

Animals↗

PubMed1977

Heterotopic cardiac transplantation with a xenograft for assistance of the left heart in cardiogenic shock after cardiopulmonary bypass.

One of the indications for the use of the heterotopic cardiac transplant is temporarily to support a failing heart in the anticipation of its recovery when all other measures of support have been unsuccessful. Human donors are not always available when required and we decided to use a xenograft for this purpose when the need arose. This report details our experience with a baboon and a chimpanzee cardiac xenograft transplant in the heterotopic position. We have found (a) that the operation is technically feasible; (b) that the xenograft will support the failing circulation, but that the more support required, the bigger the xenograft should be and the species chosen accordingly; (c) that severe acute rejection will occur within 4 days and the procedure should therefore only be employed where there is evidence that the patient's own heart function will recover rapidly.

Adult↗

PubMed1976

[Pig skin xenograft in burns. I. Technology, laboratory studies. II. Clinical experience].

The technology of the preparation of certainly sterile xenograft--pig's skin has been examined by the authors before the therapeutical use. On the basis of their examinations it was found by the authors that 2500 krad gamma radiation is suitable for the sterilization of the pig's skin--for the preparation of both the nature or lyophilized skin--since at this radiation value the pig's skin suffers no injury. After the preparation of the xenograft its clinical use has been initiated with certainly sterile material in children with burns. Xenograft has been used on 50 occasions, chiefly after surgical necrectomy, as provisional biological dressing. On the basis of their satisfactors results the authors advocate the use of the xenograft in burns, in certain skin affections, in clinical pictures concomitant with skinning and cutaneous necrosis and generally in all cases, in which skin grafting in necessary.

Animals↗

PubMed2026

Establishment and Characterization of Patient-Derived Xenograft Organoids for Personalized Treatment of Castration-Resistant Prostate Cancer.

BACKGROUND: Basic research on castration-resistant prostate cancer (CRPC) is limited by the lack of clinically relevant models. This study aimed to establish patient-derived xenografts (PDX) and PDX-derived organoids from clinical CRPC specimens to develop a bidirectional experimental platform for in vivo xenografts and ex vivo organoids. METHODS: We established a new PDX library (KUCaP PDX series) using CRPC clinical specimens and derived prostate cancer organoids. Comprehensive biological characterization of clinical specimens, PDXs, PDX-derived organoids, and organoid-derived xenografts (ODXs) was performed to confirm the preservation of the original tumor features. Using our PDX library, we conducted genetic engineering and drug testing to explore novel therapeutic approaches. RESULTS: PDX-derived organoids were successfully established from all eight KUCaP PDX lines (100%). Four of the eight lines (50%) were maintained during the long-term culture experiments for over ten passages. Key features observed in the original clinical specimens, including genetic alterations and castration responsiveness, were maintained across the PDX, PDX-derived organoid, and ODX models. RNA sequencing revealed that transcriptomic profiles were consistently maintained across clinical specimens, PDXs, PDX-derived organoids, and ODXs. One PDX and organoid (KUCaP19) which exhibited a high homologous recombination deficiency (HRD) score, without any pathogenic homologous recombination repair (HRR) gene alterations, showed sensitivity to a poly ADP-ribose polymerase (PARP) inhibitor. In contrast, KUCaP12, which had no HRR alterations and a low HRD score, did not respond to PARP inhibition. CONCLUSIONS: We developed the KUCaP library as a novel experimental platform for CRPC research by integrating clinical specimens with PDX, organoid, and ODX models along with their genomic and transcriptomic data. These models largely retained the genetic profiles and responses to castration observed in the original tumors. The bidirectional use of personalized PDX and organoids will facilitate the elucidation of the molecular mechanisms of CRPC.

Male↗

PubMed1977

Sequential hemodynamic studies in patients having aortic valve replacement with the Ionescu-Shiley pericardial xenograft.

Sequential hemodynamic studies were performed in 13 patients having aortic valve replacement with glutaraldehyde-stabilized pericardial xenografts. The investigation done preoperatively was repeated twice in all patients at mean intervals of 9.9 and 42.2 months following valve replacement. Annulus diameters of the valves were 19, 23, and 25 mm. Between the preoperative and the first postoperative investigation there was a significant increase in cardiac index (p less than 0.05) and a significant reduction in both pulmonary wedge and left ventricular end-diastolic pressures (p less than 0.01). At the first postoperative study the mean ejection systolic gradient across the three sizes of aortic pericardial xenograft was 7, 15.7, and 8.4 mm Hg at rest and 10, 19.6, and 13.7 mm Hg on exercise, respectively. The corresponding surface areas of the three valve sizes were 1.1, 1.5, and 1.62 cm2 at rest and 1.4, 2.1, and 2.03 cm2 on exercise. There was no significant change in any of these measurements between the first and the second postoperative study. The results have shown considerable postoperative hemodynamic improvement, insignificant transvalvular pressure gradients, and maintenance of the functional integrity of the pericardial xenograft up to 56 months following valve insertion.

Adult↗

PubMed1979

Serological aspects of rat tumour xenograft growth in athymic nude mice.

The serum of athymic nude mice bearing rat tumour xenografts has been examined for tumour-specific antigen. With a sarcoma and a hepatoma, tumour-specific antigen expression continued in xenograft growths, and sera of tumour-bearing mice contained free antigen, assayed by its ability to neutralise reactivity of tumour-immune rat sera against tumour target cells in an indirect membrane-immunofluorescence test. In contrast, no anti-rat antibody was detectable in sera of mice bearing the xenografts, or rejecting cells injected in admixture with BCG.

Animals↗

PubMed1977

The use of porcine xenografts on nail beds following total nail avulsion and phenol chemomatrixectomy.

The success of applying split-thickness porcine xenografts to nail beds after nail avulsion with matrix chemocauterization depends on the adherence of the graft to the underlying tissue. When this was obtained, the authors found that porcine xenografts contribute markedly toward reducing postoperative pain and drainage. Further investigation is being undertaken to determine whether total healing time following chemomatrixectomy has been reduced by utilizing xenografts.

Animals↗

PubMed2025

An Annotated Biobank of Triple-Negative Breast Cancer Patient-Derived Xenografts Features Treatment-Naïve and Longitudinal Samples during Neoadjuvant Chemotherapy.

UNLABELLED: Triple-negative breast cancer (TNBC) that fails to respond to neoadjuvant chemotherapy (NACT) can be lethal. Developing effective strategies to eradicate chemoresistant disease requires experimental models that recapitulate the heterogeneity characteristic of TNBC. To that end, we established a biobank of 92 orthotopic patient-derived xenograft (PDX) models of TNBC from the tumors of 75 patients enrolled in A Robust TNBC Evaluation fraMework to Improve Survival clinical trial (ARTEMIS, NCT02276443), including 12 longitudinal sets generated from serial patient biopsies collected throughout NACT treatment and from metastatic disease. Models were established from both chemosensitive and chemoresistant tumors, and nearly 30% of the PDX models were capable of metastasizing to the lungs. Comprehensive molecular profiling demonstrated conservation of genomes and transcriptomes between patient and corresponding PDX tumors, with representation of all major transcriptional subtypes. Transcriptional changes observed in the longitudinal PDX models highlighted dysregulation in pathways associated with DNA integrity, extracellular matrix interactions, the ubiquitin-proteasome system, epigenetics, and inflammatory signaling. These alterations revealed a complex network of adaptations associated with chemoresistance. Overall, this PDX biobank provides a valuable tool for tackling the most pressing issues facing the clinical management of TNBC. SIGNIFICANCE: The development of a patient-derived xenograft biobank that comprehensively captures the genomic and transcriptional diversity of triple-negative breast cancer promises to be a robust resource to investigate and overcome chemoresistance and metastasis.

Animals↗

PubMed2026

A Patient-Derived Xenograft Repository Capturing Clinical and Molecular Heterogeneity of Large B-cell Lymphoma.

UNLABELLED: Large B-cell lymphomas (LBCL) are a clinically and molecularly diverse group of malignancies with a rapidly evolving therapeutic landscape that has introduced new areas of clinical need, such as post-CD19 chimeric antigen receptor T (CART19) progression. Patient-derived xenograft (PDX) models are an important tool for mechanistic studies and preclinical evaluation of new therapies and can be generated from a variety of clinical contexts that capture tumor-intrinsic resistance mechanisms. We therefore undertook a comprehensive effort to generate PDX models that encompass the molecular landscape of LBCLs and include important clinical scenarios for new drug development. Here, we describe the first 48 models within this publicly available repository, capturing the transcriptional and genetic subsets of LBCL. These models also include 23 generated from post-CART19 progression patient biopsies, which reproduce patterns of progression driven by CD19 mutation or expression loss, as well as tumor cell-intrinsic CART19 resistance that we validated in vivo. SIGNIFICANCE: Here, we describe X-LYMPH (Xenografts of Lymphoma), a publicly available and molecularly annotated PDX repository that captures the heterogeneity of LBCL. X-LYMPH includes models of CAR T-cell resistance, providing a shared foundation for mechanistic research and therapeutic development for lymphomas. See related commentary by Evgin and Steidl, p. 655.

Humans↗

PubMed1979

Transseptal and retrograde left ventricular catheterization in patients with the stent-mounted porcine xenograft valve prosthesis in the aortic position.

Cardiac catheterization techniques for measuring the systolic pressure gradient across the stent-mounted porcine xenograft in the aortic position and accomplishing left ventriculography are described. The transseptal technique is a rapid and predictable means of entering the left ventricle but requires a highly skilled operator. Retrograde left ventricular catheterization via the femoral artery is a technique familiar to all invasive cardiologists. Usually a pitfall catheter is used. In patients with the stent-mounted procine xenograft in the aortic position, we have found the A2 Multipurpose catheter to be the fastest and most predictable means of entering the left ventricle from the groin. Potential complications of retrograde left ventricular catheterization in patients with aortic valve prostheses are discussed.

Aortic Valve↗

PubMed1979

Structure-related thrombosis involving a porcine xenograft valve.

A patient developed acute congestive heart failure following chordal rupture and underwent mitral valve replacement with a porcine xenograft. He recovered adequate hemodynamic function but died one month later with widespread bronchopneumonia. Postmortem examination revealed a prominent muscular shelf in the right coronary leaflet of the xenograft, and focal thrombosis involving the adjacent sewing ring and left atrial wall. The location of the thrombus suggests that it formed as a result of local stasis behind the large muscular shelf. Limiting the size of this muscular shelf by valve selection and construction may reduce the thrombogenicity of this prosthesis.

Bioprosthesis↗

PubMed1978

BCG treatment of human tumour xenografts in athymic nude mice.

Xenografts of 3 human malignant cell lines in congenitally athymic nude mice have been examined for susceptibility to BCG. Growth of all 3 tumours, a bladder carcinoma, a melanoma and a colon carcinoma, was suppressed when cells were injected in admixture with BCG. Distant injection of BCG was ineffective. Mice with progressive growths had no detectable anti-human antibody, and rejection of cells and BCG failed to confer protection against subsequent tumour challenge. These studies indicate that human malignant cells are susceptible to local BCG-activated host responses, and that athymic mouse xenografts may be a useful model for assessing the response of human tumours to such agents.

Animals↗

PubMed1979

Influence of biogenic amines on the growth of xenografted human colorectal carcinomas.

The influence of some biogenic amines and amine-receptor-blocking drugs in the growth rate of human colorectal carcinomas propagated as s.c. xenografts in immune-deprived mice was studied. In mice treated with adrenaline, a beta-adrenergic agonist, the growth of xenografts was suppressed for 2 days, after which growth was resumed at a rate similar to that in control animals. Treatment with the phosphodiesterase inhibitor theophylline prolonged the adrenaline-induced inhibition of growth. Treatment with the beta-adrenergic antagonist sotalol or practolol increased the rate of tumour growth. Treatment with either serotonin or the histamine H2-receptor agonist Dimiprit had no effect on tumour growth rate. However, the antiserotoninergic drug BW 501C and the histamine H2-receptor antagonist cimetidine each caused short-term suppression of tumour growth.

Adrenergic Agonists↗

PubMed1975

Dacron conduit with a stented porcine xenograft valve in the anatomic correction of transposition of the great arteries and subpulmonary stenosis.

A stented porcine xenograft valve, sutured into a woven Dacron tubular graft, has been used in the anatomic correction of D-loop, D-transposition of the great arteries, and subpulmonary stenosis. The main advantage of this technique is its simplicity and practicality, as both Dacron tubular grafts and stented porcine xenograft valves are commercially available.

Adolescent↗

PubMed1979

Growth of human tumor xenografts implanted under the renal capsule of normal immunocompetent mice.

The subrenal capsule technique proved effective in demonstrating that the growth of human tumors in normal, immunocompetent animals for 6 days was quantifiable in ocular micrometer units. Positive growth was demonstrable not only with human tumors that had been established in serial transplantation in athymic nude mouse hosts, but also with primary surgical explants. Growth rates of transplantation-established xenograft systems were similar whether implanted in athymic nude or in normal immunocompetent animals indicating that the 6-day time-frame successfully evades growth inhibitory effects of immunologic origin. Immunosuppression with a single dose of cyclophosphamide did not appear to affect growth rate, but permitted the tumors to grow larger extending the time to reach peak size. Significantly, xenografts of primary surgical explants showed positive growth more frequently in 6 days (82%) in the immunocompetent animal than in 11 days (30%) in the immunodeficient athymic nude mouse.

Animals↗