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Results for “SCID mouse”

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At least 217 records · Page 12Linked to original sources
PubMedDate not supplied

Prevention of peritoneal carcinomatosis from human gastric cancer cells by adjuvant-type intraperitoneal immunotherapy in a SCID mouse model.

PURPOSE: We analyzed the effect of intraperitoneal immunotherapy in an animal model mimicking locoregional dissemination of tumor cells during resection of advanced tumors. METHODS: We first established a tumor model with human gastric cancer cells (MKN-45) in the peritoneal cavity of CB-17-SCID mice. Three hours following the injection of tumor cells into the peritoneal cavity, mAb 17-1A alone and in combination with human LAK cells were given intraperitoneally at different dosages. The results were quantified by determining the weight of the peritoneal tumor masses. RESULTS: After intraperitoneal administration of 17-1A mAb, a tumor reduction could be shown (median tumor mass after 10 microg mAb: 171 microg; after 100 microg: 130 microg) when compared with the control group (632 microg). Following a combined therapy with mAb and LAK cells, a statistically significant tumor reduction could be observed (after 10 microg mAb + 20-50 x 10(6) LAK cells: 80 microg; after 100 microg mAb + 20-50 x 10(6) LAK cells: 12 microg, p = 0.0005). With specific dosages of antibody and LAK cells it was even possible to achieve complete tumor clearance. CONCLUSIONS: Intraperitoneal immunotherapy reduces the peritoneal tumor masses and can even prevent the peritoneal carcinomatosis formation.

Animals↗
PubMed1996

Inhibitory effect of a Pichia anomala killer toxin on Pneumocystis carinii infectivity to the SCID mouse.

A Pichia anomala killer toxin has been demonstrated to have a specific inhibitory effect on the in vitro attachment of Pneumocystis carinii. The results presented herein show that this yeast toxin is also effective against P. carinii infectivity in reducing parasite colonization in the lungs of SCID mice. The specificity of this inhibitory effect was controlled using a monoclonal antibody neutralizing the killer properties of the yeast toxin.

Animals↗
PubMed2000

The diversity of antigen-specific antibodies in humans and in two xenochimeric SCID mouse models.

We applied two-dimensional gel electrophoresis (2-DE) to study the repertoire of tetanus toxoid (TT)-specific antibodies produced after TT immunization in healthy humans and in severe combined immunodeficient mice xenotransplanted with either human peripheral blood leukocytes (PBLe) or with human adult tonsil (hu-ton) pieces. Specific anti-TT antibodies, as well as total immunoglobulins (Ig), were purified by affinity chromatography on TT-Sepharose or Protein G-Sepharose, respectively. 2-DE unambiguously allowed us to differentiate between the specific humoral responses produced either by humans or by the two xenochimeric mouse models. Anti-TT antibodies produced by humans were polyclonal with a superimposed oligoclonality that was donor-dependent and that did not change upon time. By contrast, immunized hu-PBLe-SCID mice exhibited an evident clonal restriction of the Ig, which increased with time after boosting. Hu-ton-SCID mice showed a clonal diversity which was intermediate between those observed in humans and in hu-PBLe-SCID mice, and which was stable over time. In addition, information was gained by 2-DE, correlating with data obtained by enzyme-linked immunosorbent assay (ELISA), on the isotype composition of the anti-TT IgM response. Altogether, our results clearly demonstrated that the clonal diversity of monospecific antibodies can be appreciated by 2-DE, and that the largest diversity was found in humans when compared to that in xenochimeric models. In addition, mice implanted with pieces of lymphoid organs had the broadest anti-TT Ig diversity, an observation supporting the use of this model for the generation of antibodies with restricted specificity.

Animals↗
PubMed1993

Herpetic stromal keratitis in the reconstituted scid mouse model.

Infections of the cornea with herpes simplex virus type 1 cause inflammatory lesions which frequently lead to blindness. The disease is suspected to be immunopathological in nature. To establish this point and to study possible mechanisms involved, corneal infections in C.B-17 scid/scid and cell-reconstituted scid mice were investigated. Whereas unreconstituted scid mice failed to develop herpetic stromal keratitis (HSK) and died of encephalitis, mice reconstituted with T lymphocytes generated severe lesions. T cells of the CD4+ subset were found to be essential mediators of the HSK lesion, while T cells of the CD8+ subset protected mice from lethality. The results confirm that HSK is an immunopathological disease and that scid mice provide a convenient model that should prove valuable in establishing the biochemical mechanisms by which HSK is mediated.

Animals↗
PubMed1999

Characterization of human ovarian carcinomas in a SCID mouse model.

This study characterizes a murine model which is promising for the study of the growth and natural history of ovarian cancer and for testing of new therapies for its treatment. Intact portions of 20 different human ovarian cancer surgical specimens were implanted in over 60 severe combined immunodeficient (SCID) mice using techniques previously developed in our laboratory. Growth of xenografts was evaluated by gross examination and histopathologic analysis. Confirmation of the human origin of the tumor outgrowth was obtained using in situ hybridization analysis. By histological evaluation, all of the patients' tumors showed evidence of invasive growth in at least 1 of the mice implanted with portions of each surgical specimen and these tumors remained morphologically similar to the parent tumors for a long period of time. Furthermore, 65% (13/20) of the xenografts grew rapidly enough (i.e., reached a diameter of 1-2 cm within 2-6 months) to allow passage to subsequent SCID mice. Among the passaged xenografts, 3 eventually developed metastases in a distribution pattern similar to that of naturally occurring ovarian cancer and 2 developed ascites without evidence of further metastatic spread. Upon evaluation of sera from tumor-bearing mice, human antibodies presumably derived from immunoglobulin-secreting cells present in the original tumor specimen were identified. In support of this, human B cells and plasma cells could be seen within the tumor xenograft for more than 6 months following implantation. In summary, transplantation of surgical specimens from ovarian cancer patients into SCID mice results in an attractive model for the study of the natural history of ovarian cancer and may also be useful for analysis or new experimental therapeutic approaches for the treatment of this disease.

Animals↗
PubMed2003

Transfer of alopecia areata in the human scalp graft/Prkdc(scid) (SCID) mouse system is characterized by a TH1 response.

Alopecia areata is an autoimmune condition directed at hair follicles, which results in loss of hair. We have previously demonstrated that it is possible to transfer hair loss, along with the immunohistologic findings of alopecia areata, to human scalp grafts on Prkdc(scid) (SCID) mice by injection of autologous activated lesional T-cells. This study examines the cytokine profile of T-cells and follicular epithelium following transfer of hair loss. Two consistent findings significantly (P < 0.01) associated with hair loss were production of interferon-gamma-inducible protein-10 kDa (IP-10) by follicular epithelium (13/13), and production of INF-gamma by infiltrating T-cells (10/12). Noninjected control grafts regrew hair, and were generally negative for IP-10 (positive 2/9), and INF-gamma (positive 2/9), but expressed of IL-10 on the follicular epithelium (7/9). These data support an INF-gamma TH1 pathogenesis for hair loss in alopecia areata.

Alopecia Areata↗
PubMed2003

Treatment of human promyelocytic leukemia in the SCID mouse model with cotylenin A, an inducer of myelomonocytic differentiation of leukemia cells.

Cotylenin A has differentiation-inducing activity in human myeloid leukemia cell lines and leukemic cells that were freshly isolated from acute myeloid leukemia (AML) patients in primary culture. Injection of the human promyelocytic leukemia cell line NB4 into SCID mice resulted in the death of all mice due to leukemia. Administration of cotylenin A significantly prolonged the survival of mice inoculated with NB4 cells. In an in vivo analysis, cotylenin A induced the differentiation of leukemia cells in a retinoid-resistant leukemia model. Cotylenin A may be useful for differentiation therapy of retinoid-resistant leukemia.

Animals↗
PubMedDate not supplied

Plasmodium falciparum: production of human antibodies specific for the MSP-3 protein in the Hu-SPL-SCID mouse.

Human immunity against Plasmodium falciparum malaria is mediated by IgG antibodies. One of the major targets of protective antibodies is the MSP-3 protein. Anti-MSP-3 human monoclonal antibodies could therefore be valuable for passive immunotherapy, particularly of drug resistant malaria. Human monoclonal antibodies were previously produced in the Hu-SPL-SCID model reconstituted with human splenocytes, immunized by highly immunogenic neo-antigen or a recall antigen. We report here that this model can also be successfully employed to induce human antibody-secreting cells specific of low immunogenicity neo-antigens, such as MSP-3. These cells represent a new and valuable source of human monoclonal anti-malaria antibodies.

Animals↗
PubMedDate not supplied

Visualisation of neuroblastoma growth in a Scid mouse model using [18F]FDG and [18F]FLT-PET.

BACKGROUND: Tumor therapy has been monitored using the metabolic indicator [18F]fluorodeoxyglucose ([18F]FDG). However, the nucleotide precursor [18F]fluoro-thymidine ([18F]FLT) is in principle more specific as it is incorporated into DNA. Thus, the [18F]FDG and [18F]FLT uptake by human neuroblastomas grown in Scid mice are compared in this study. MATERIALS AND METHODS: Scid mice were inoculated with human neuroblastoma cells. Tumor imaging was performed with a human whole-body full-ring PET scanner. Furthermore, the tumor weight and the cell proliferation rate were determined. RESULTS: Neuroblastomas could be visualised using [18F]FDG in 40% and with [18F]FLT in 70% of the cases. [18F]FDG or [18F]FLT uptake could not be visualised in neuroblastomas less than 1.0 g in weight. No correlation between the cell proliferation rate and tracer uptake could be detected. CONCLUSION: [18F]FLT showed a higher uptake than [18F]FDG and, therefore, might be more suitable for monitoring anticancer therapy, at least in this tumor model.

Animals↗
PubMedDate not supplied

Maintaining squamous epithelial architecture in a human cervical epithelium to SCID mouse xenograft model system.

OBJECTIVE: To establish a mouse model system of human cervical epithelium that maintains the stratified squamous architecture overlying a well-defined basement membrane. METHODS: Normal cervical tissue specimens were obtained from the transformation zone of hysterectomy specimens. Small (2 mm) cubes of tissue containing stroma and epithelium were placed subdermally into severe combined immunodeficient (SCID) mice and harvested between 7 and 45 days. Specimens were examined histologically for the presence of stroma, epithelium, and basement membrane. RESULTS: In 49 xenograft attempts in 24 mice, 35 (71%) were identified microscopically. Of these, 28 (80%) had identifiable epithelium and 20 (57%) formed cysts lined with stratified squamous epithelium. A cuboidal basal layer clearly defined the basement membrane. Proliferation within the cyst epithelium was demonstrated by expression of the Ki67 proliferation marker and the presence of mitotic figures. CONCLUSIONS: A human to mouse xenograft model system is described that maintains, in high yield, stratified squamous epithelium overlying a well-defined basement membrane. Advantages of this model system include the following: (1) The tissue originates from readily available human specimens; (2) A stratified squamous epithelial architecture is maintained for a sufficient time to study viral effects on proliferation; (3) The basement membrane of the epithelium is well defined, allowing for investigation of connective tissue factors in cervical intraepithelial neoplasia and cervical cancer.

Animals↗
PubMed2002

The humanized SCID mouse model to study HLA class II-linked autoimmunity to desmoglein 3 in pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris (PV) is a severe autoimmmune skin disorder induced by antibodies against desmoglein (Dsg) 3 on epidermal keratinocytes. OBJECTIVES: To establish an active animal model of PV to analyse the T-cell-regulated production of pathogenic antibodies in vivo. METHODS: Immunodeficient SCID mice were injected with peripheral blood lymphocytes (PBL) from an HLA-DRB1*0402/DQ8+ patient with PV or a DRB1*0402/DQ8+ healthy donor, with or without subsequent injections of human Dsg3 or preincubation of PBL with Dsg3. RESULTS: Human immunoglobulins (2.7-18.5 mg mL-1) were detected in all the mice after 8 weeks. Only one of 30 PBL-treated mice developed IgM against Dsg3 and showed intercellular IgM deposits in skin, nostrils and tongue. In contrast, in a previous study, 41% of SCID mice injected with PBL from patients with PV developed anti-Dsg3 antibodies in vivo. CONCLUSIONS: Our inability to reproduce these findings may be due to the transfer of slightly lower numbers of PBL (20 x 10(6) vs. 25-30 x 10(6)).

Animals↗
PubMed1997

Preservation of functioning human thyroid "organoids" in the scid mouse. IV. In vivo selection of an intrathyroidal T cell receptor repertoire.

To study the in vivo influence of thyroid cells on the T cell receptor repertoire in human autoimmune thyroid disease, we mixed lymphocyte-free thyrocytes (approximately 1.2 x 10[6]) from patients with Graves' disease with autologous peripheral blood mononuclear cells (PBMC; approximately 1.5 x 10[6]) and transplanted this mixture sc into scid mice while suspended in a basement membrane gel (approximately 0.4 ml). Controls included mice that received either thyrocytes only or PBMC only. The resulting artificial mixed cell thyroid organoids were explanted after 5 weeks, and their T cell receptor repertoire was examined. Of a total of 63 organoids constructed, 60 were recovered (95.2%). Total RNA was extracted and then analyzed by reverse transcription-PCR primarily for human T cell receptor (hTcR) Vbeta gene expression using 21 hTcR Vbeta amplimers. A restricted pattern of hTcR Vbeta gene expression was found, with 6 Vbeta genes (Vbeta5, 6, 7, 8, 13.1, and 18) predominantly expressed [P < 0.05, by ANOVA on ranks and Student-Newman-Keul's (SNK) test]. PBMC and control organoids showed no preferential selection of particular hTcR V gene-expressing T cells. This reductionist, mixed cell, thyroid model reflected earlier observations in human and murine autoimmune thyroid diseases in which a bias in hTcR V gene family expression had been observed. The model permitted in vivo T cell selection and/or enrichment of potentially disease relevant human T cells.

Animals↗
PubMed2002

Passive transfer of serum antibodies induced by BBG2Na, a subunit vaccine, in the elderly protects SCID mouse lungs against respiratory syncytial virus challenge.

Respiratory syncytial virus (RSV) is responsible for severe low respiratory tract infections in young infants and the elderly. To investigate whether BBG2Na, a recombinant subunit vaccine comprising aa 130-230 of the RSV G protein, induced protective Abs in subjects over 60 years during phase II clinical trial, pre- and postimmunization sera of individuals immunized with BBG2Na or placebo were transferred into SCID mice before RSV challenge. These sera dose-dependently reduced lung RSV titers. However at some points of serial dilutions, postimmunization sera of BBG2Na-immunized subjects only were significantly more efficient than the corresponding preimmunization sera, in agreement with the induction of an increased Ab response against multiple epitopes on RSV-A G protein. Thus, BBG2Na is immunogenic in the elderly and confers passive protection in mice after serum transfer. To our knowledge, this is the first description of protective Abs induced by a subunit vaccine in human.

Administration, Intranasal↗
PubMed2006

c7E3 Fab inhibits human tumor angiogenesis in a SCID mouse human skin xenograft model.

The alphavbeta3 integrin plays an important role in tumor growth and angiogenesis. Inhibition of this receptor by intact bivalent antibodies has been shown to inhibit angiogenesis and tumor growth. In this study we tested the chimeric Fab of 7E3 (c7E3 Fab), an antibody reactive with human platelet GPIIb/IIIa and alphavbeta3 to determine if it would inhibit in vivo angiogenesis and tumor growth in a SCID mouse/human skin tumor growth and angiogenesis model. c7E3 Fab inhibited human tumor angiogenesis and tumor growth. These data suggest monovalent antibody fragments devoid of antibody effector function can have efficacy in preclinical models of angiogenesis.

Abciximab↗