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Results for “Neoplasms, Complex and Mixed”

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PubMed1978

Response of tumour-related and normal lymphocytes to antigens on fibroblasts from embryos of varying age.

The in vitro cytotoxic immune response of spleen lymphocytes from primiparous and tumour-related mice to embryonic cells from embryos of varying age and tumour cells has been investigated. The results indicate that lymphocytes from both primiparous and tumour-related (i.e., tumour-bearing or tumour-excised) animals give a response which is greater than that from cells from control mice ("virgin cells"). Moreover, in this putative anamnestic response the immune cells detect antigenic differences in the cell populations of embryos of varying age, which are not as readily demonstrable when cytotoxicity is derived from virgin cells. As a further indication of the in vivo priming to embryo-assoicated antigens, the data show that the precursors of cytotoxic cells apparently undergo a blastogenic response in the presence of embryo antigen, and revert to small quiescent cells when antigen is removed, in a way entirely analogous to that described for reactivity of mixed leucocyte cultures to antigens of the major histocompatibility complex. Finally, it seems that in animals immediately after removal of embryonic antigen (and to a lesser degree in virgin or late-embryo-immune mice) there exists a suppressor cell population which inhibits an anti-embryo cytotoxic response far more than an antiallograft response.

Animals↗

PubMedDate not supplied

Altered CD8(+) T-cell responses when immunizing with multiepitope peptide vaccines.

Efforts to develop effective cancer vaccines often use combinations of immunogenic peptides to increase the applicability and effectiveness of the immunizations. The immunologic consequences of combining more than 1 self/tumor antigen in a single vaccine emulsion remain unclear, however. We performed 2 sequential clinical trials in patients at high risk for melanoma recurrence. Patients were given the highly immunogenic gp100:209-217(210M) peptide and the less immunogenic tyrosinase:368-376(370D) peptide once every 3 weeks for 4 weeks. This vaccination course was 12 weeks long, and patients were vaccinated for up to 4 courses (16 total vaccinations). In the first trial in 31 patients, the peptides were emulsified separately in incomplete Freund adjuvant and injected at 2 different sites. In the second trial in 33 patients, the peptides were emulsified together and injected at the same site. Cryopreserved lymphocytes were obtained by apheresis after each course and were evaluated for antipeptide activity using tetramer, enzyme-linked immunospot, and in vitro sensitization boost assays. When the peptides were injected at separate sites, robust specific reactivity to the native gp100:209-217 peptide was measured by each of the assays, whereas immunization with the tyrosinase:368-376(370D) peptide was far less effective. When the peptides were emulsified and injected together at the same site, immunization to the gp100:209-217(210M) epitope dropped precipitously, whereas reactivity to the tyrosinase:368-376(370D) peptide was enhanced. These cautionary data indicate that mixing peptides in the same emulsion can alter reactivity compared with peptides injected separately by mechanisms that may include the induction of localized nonspecific inflammation or competitive binding of peptides to major histocompatibility complex molecules.

Adult↗

PubMed2006

Dosimetric comparison of two different three-dimensional conformal external beam accelerated partial breast irradiation techniques.

PURPOSE: We compare the dosimetry of two techniques for three-dimensional, conformal, external beam, accelerated partial breast irradiation (3D-CPBI) in the supine position. METHODS AND MATERIALS: Sixteen patients with Stage I breast cancer had PBI treatment plans generated using the multiple, noncoplanar photon field technique and the three-field, mixed-modality technique. Planning target volumes (PTVs; lumpectomy site plus 1.5-2.0 cm margin) and total dose (32 Gy) were held constant to facilitate dosimetric comparisons. Plans were optimized for conformality and PTV coverage. RESULTS: Mixed-modality plans employed fewer fields than multiple, noncoplanar photon field plans (mean 3.2 vs. 4.1). Both techniques provided comparable PTV coverage and in all cases, 95% of the PTV received 90% of the prescribed dose. Volumes of ipsilateral breast receiving greater than 16 Gy were similar; however, the mean volume of ipsilateral breast receiving 8 Gy was significantly lower for mixed-modality plans (58% vs. 66%). No differences in the volumes of ipsilateral lung or heart receiving greater than 5 Gy were observed, however, the mixed-modality technique delivered 2.5 Gy to larger volumes of these organs. CONCLUSIONS: Both techniques for supine position, 3D-CPBI provides excellent normal tissue sparing with adequate PTV coverage. The multiple, noncoplanar photon field technique exposes smaller volumes of ipsilateral lung and heart to low dose radiation at the expense of increased plan complexity and larger irradiated breast volumes.

Adult↗

PubMed2000

[Study on recombinant BCG to prevent infections of intracellular pathogens].

Studies on recombinant BCG (rBCG) which my group carried out so far were reviewed. Recombinant BCG which secreted alpha antigen-fused foreign antigen was constructed and tested for its ability to induce protective immunity. Thus, rBCG secreting merozoite surface protein 1 (MSP1) of Plasmodium yoelii efficiently protected the infection more than recombinant MSP 1 mixed with artificial adjuvant RAS or IFA did. rBCG which secreted excess amounts of antigen 85 complex A inhibited the multiplication of M. leprae in the footpads of mice. rBCG which secreted alpha antigen-fused IL-2 stimulated peritoneal exudate cells of mice resulting in enhancing killing a bladder cancer cell line in vitro.

Animals↗

PubMed1985

Differential gamma-interferon response of human colon carcinoma cells: inhibition of proliferation and modulation of immunogenicity as independent effects of gamma-interferon on tumor cell growth.

The effect of recombinant gamma-interferon (IFN-gamma) on established human colon carcinoma cell lines as well as fresh tumor cells from colon carcinoma patients has been investigated with respect to growth inhibition, enhancement of HLA expression, and modulation of immunogenicity. A direct antiproliferative activity of IFN-gamma was observed in five of seven cell lines tested, with a reduction of [3H]thymidine incorporation between 30 and 90%. Depending on the cell line, the IFN-gamma doses required for maximal inhibition varied between 20 and 2 X 10(4) units/ml. Independent of this effect, IFN-gamma enhanced the expression of HLA-A,B,C antigens in all cells investigated and induced expression of HLA-DR in three of seven carcinoma cell lines. Antigenic modulation of Class I and II major histocompatibility complex antigens was paralleled by an enhancement of the in vitro immunogenicity in three of four established carcinoma lines and in three of three cases, using cells derived from primary tumor cultures. Induction or enhancement of both proliferative and cytolytic T-cell responses was obtained in allogeneic and in autologous mixed-lymphocyte tumor cell cultures.

Adenocarcinoma↗

PubMed1985

Skeletal muscle actin as tumor marker in the diagnosis of rhabdomyosarcoma in childhood.

Immunoaffinity-purified and tissue-specific antibodies against carp skeletal muscle actin have been assessed for their usefulness in diagnosing rhabdomyosarcoma. Routinely processed formaldehyde-fixed tissue and the avidin--biotinyl--peroxidase complex technique were used. Thirty-six tumors of patients varying in age from less than 1 year to 17 years were diagnosed as rhabdomyosarcoma on the basis of routine histological stains or electron microscopy, and on clinical grounds. Among them were 20 poorly differentiated tumors. All moderately and well-differentiated rhabdomyosarcomas and the majority of the poorly differentiated tumors (13 of 20) showed positive immunostaining for actin. Positive staining was observed in all three types of rhabdomyosarcoma, i.e., embryonal, alveolar, and pleomorphic. Besides rhabdomyosarcomas, the only other positive neoplasms were those that contained rhabdomyoblastic differentiation such as malignant "triton" tumors and malignant mixed müllerian tumors. Our results indicate that antibodies against skeletal muscle actin are a powerful tool for diagnosing rhabdomyosarcoma and that they can be used to distinguish the poorly differentiated forms from other types of small round cell tumors in childhood such as neuroblastoma, Ewing's sarcoma, and malignant lymphoma. The results are discussed in the light of the embryogenesis of cross-striated skeletal muscle.

Actins↗

PubMed1989

Ability of p53 and the adenovirus E1b 58-kilodalton protein to form a complex is determined by p53.

We have investigated p53-E1b 58-kilodalton (kDa) protein complex formation during permissive and semipermissive infections with adenovirus type 5 (Ad5) dl309. While metabolic labeling studies easily detected p53-E1b 58-kDa protein complexes in transformed rat cells (XhoI-C), the same methods have not revealed complexes during infection of either human osteosarcoma cells (permissive) or normal rat kidney cells (semipermissive). Complexes were not detectable at any stage during the replicative cycle of Ad5 dl309 in osteosarcoma cells, and they could not be stabilized by using an in vivo cross-linking agent. In addition, using the E4-defective mutant Ad5 dl355, no complexes were observed either. Thus, the lack of p53-E1b 58-kDa protein complex formation during infection is not due to competition from the E4 34-kDa protein. In vitro association experiments showed that in vitro-translated mouse and human p53 could form complexes with E1b 58-kDa antigen expressed during infection. Thus, such E1b proteins are competent to form complexes. The converse experiment, in which in vitro-translated E1b 58-kDa protein was mixed with lysates of osteosarcoma cells, showed little or no p53-E1b 58-kDa protein association, even though the in vitro E1b 58-kDa protein could associate stably with p53 from cells containing endogenous p53-E1b 58-kDa protein complex. These data suggest that competence to form p53-E1b 58-kDa protein complexes resides in some property of p53.

Adenovirus Early Proteins↗

PubMed2006

Multivariable modeling of radiotherapy outcomes, including dose-volume and clinical factors.

PURPOSE: The probability of a specific radiotherapy outcome is typically a complex, unknown function of dosimetric and clinical factors. Current models are usually oversimplified. We describe alternative methods for building multivariable dose-response models. METHODS: Representative data sets of esophagitis and xerostomia are used. We use a logistic regression framework to approximate the treatment-response function. Bootstrap replications are performed to explore variable selection stability. To guard against under/overfitting, we compare several analytical and data-driven methods for model-order estimation. Spearman's coefficient is used to evaluate performance robustness. Novel graphical displays of variable cross correlations and bootstrap selection are demonstrated. RESULTS: Bootstrap variable selection techniques improve model building by reducing sample size effects and unveiling variable cross correlations. Inference by resampling and Bayesian approaches produced generally consistent guidance for model order estimation. The optimal esophagitis model consisted of 5 dosimetric/clinical variables. Although the xerostomia model could be improved by combining clinical and dose-volume factors, the improvement would be small. CONCLUSIONS: Prediction of treatment response can be improved by mixing clinical and dose-volume factors. Graphical tools can mitigate the inherent complexity of multivariable modeling. Bootstrap-based variable selection analysis increases the reliability of reported models. Statistical inference methods combined with Spearman's coefficient provide an efficient approach to estimating optimal model order.

Carcinoma, Non-Small-Cell Lung↗

PubMed1993

Canine mammary tumour cell lines established in vitro.

Mammary tumours are the most common tumours in the female dog. The tumours have a complex histology and exist in epithelial, mixed and mesenchymal forms. To study the biology of canine mammary tumours, five cell lines have been established and characterized. The results indicate that canine mammary tumours might be derived from mammary stem cells and that the tumour growth is independent of oestrogens. The established canine mammary tumour cell lines will be valuable tools in further studies of the histogenesis and pathogenesis of these tumours.

Animals↗

PubMed2006

Tuberous sclerosis: a syndrome of incomplete tumor suppression.

Tuberous sclerosis (TS) is a congenital neurocutaneous syndrome (or phacomatosis) characterized by widespread development of hamartomas in multiple organs. For affected individuals, neurological and psychiatric complications are the most disabling and lethal features. Although the clinical phenotype of TS is complex, only three lesions characterize the neuropathological features of the disease: cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas. The latter is a benign brain tumor of mixed neuronal and glial origin. Tuberous sclerosis is caused by loss-of-function mutations in one of two genes, TSC1 or TSC2. The normal cellular proteins encoded by these genes, hamartin and tuberin, respectively, form a heterodimer that suppresses cell growth in the central nervous system by dampening the phosphatidylinositol 3-kinase signal transduction pathway. The authors review the clinical and neuropathological features of TS as well as recent research into the molecular biology of this disease. Through this work, investigators are beginning to resolve the paradoxical findings that malignant cancers seldom arise in patients with TS, even though the signaling molecules involved are key mediators of cancer cell growth.

Animals↗

PubMedDate not supplied

A gel retardation assay system for studying protein binding to simple repetitive DNA sequences.

Simple repetitive DNA sequences have been regarded as mere "junk" present in all eukaryotic genomes. In fact, mixed simple repeat (gt)n(ga)m sequences are present in major histocompatibility complex MHC-DRB genes for long evolutionary times, including such distant animals as artiodactyla and man. We describe herein an unsophisticated method which reveals that at least certain simple repetitive (gt)n(ga)m sequences bind nuclear proteins and show characteristics of a specific DNA-protein interaction via gel retardation.

Animals↗

PubMed2001

Constitutive expression of interleukin-8 by Mutatect cells markedly affects their tumor biology.

Interleukin-8 (IL-8) is a chemokine for neutrophils and an angiogenic factor. Human tumors that express IL-8 may exhibit intense neutrophil infiltration and increased vascularization. Mutatect cells are a murine fibrosarcoma that can be grown as subcutaneous tumors in syngeneic C57BL/6 mice. Since neutrophils are a source of cytotoxic and genotoxic species, we constructed Mutatect cell lines that constitutively express human IL-8 to explore the involvement of neutrophils in tumor biology and genetic instability. An IL-8/neo expression plasmid was stably transfected into Mutatect MC17-51 cells and clone MIL-4 was isolated. Tumors initiated with 5x10(5) MIL-4 cells grew very slowly compared with tumors from pure MC17-51 cells or from 0.5 to 4x10(5) MIL-4 cells mixed with 5x10(5) MC17-51 cells. Over 95% of cells recovered from slow-growing pure MIL-4 tumors lost the transgene as measured by loss of (i) resistance to G418, (ii) expression of IL-8 protein and (iii) IL-8-specific DNA sequences. When tumors from mixed cell types were examined, loss of the transgene did not occur; rather, IL-8 producing cells appeared to have some growth advantage. The neutrophil content of tumors (as measured by myeloperoxidase) was directly proportional to the level of IL-8 expressed at the time tumors were excised. As reported earlier, the frequency of mutations at the hypoxanthine phosphoribosyltransferase locus was also directly proportional to neutrophil content. To explain some of these biological findings, we postulate that early in development of pure MIL-4 tumors, genotoxic/cytotoxic neutrophils are attracted by IL-8, which in turn leads to loss of the transgene and to localized cytotoxicity of IL-8 producing cells. In mixed tumors, where the initial IL-8 concentration may be lower, tumors might become established more readily because fewer neutrophils may be attracted. This relatively simple experimental paradigm has revealed some of the complex biological changes that can occur as a result of IL-8 in tumors.

Animals↗

PubMed1995

Immunocytochemical study of type IV collagen and laminin in canine mammary tumours.

We performed an immunohistochemical study of the basement membrane (BM) proteins laminin and type IV collagen in 35 canine mammary tumours, histologically classified according to the World Health Organization's suggested classification. Laminin and type IV collagen were seen in extracellular locations but only laminin was present in epithelial and myoepithelial cells and chondrocytes. The BM was always continuous in adenomas and fibroadenomas. In the 20 malignant tumours studied, the basement membrane was continuous in one, discontinuous in five, and virtually absent in 14. When present, the BM of malignant tumours varied in width and distribution in the same area. The benign and malignant mixed tumours did not have BM separating epithelial and newly-formed mesenchymal structures. In areas of abundant myoepithelial cells in complex and mixed tumours, both benign and malignant, there were groups of BM fragments which differed in length and thickness and occasionally formed tangles. We have called these 'membranous thickets'. Our results indicate that myoepithelial cells are the main source of the BM proteins laminin and type IV collagen in canine mammary tumours.

Adenocarcinoma↗

PubMed1987

Mycosis fungoides with mixed cryoglobulinemia and pulmonary vasculitis. A case report.

A 54 year old patient suffering from mycosis fungoides developed an immune complex disease with mixed cryoglobulinemia (type III) and pulmonary vasculitis, an association so far unreported. We believe that the pathogenesis could be ascribed to a T-cell imbalance (increase in OKT4+ cells with inversion of the OKT4/OKT8 ratio) and to a functional T-cell defect, as suggested by the reduced mitogenic responses to PHA and ConA we observed.

Cryoglobulinemia↗

PubMed1989

The expression of intermediate filaments in canine mammary glands and their tumors.

Monoclonal antibodies specific for different types of intermediate filaments (cytokeratin, vimentin, desmin and neurofilaments) were used to study the histogenesis of canine mammary glands and 57 canine mammary tumors by immunocytochemistry. The intra- and interlobular duct epithelium, acinar, and intralobular myoepithelial cells stained positively for cytokeratin. Peripheral ductal and acinar cells, as well as interstitial cells, stained positively for vimentin. A similar staining pattern was seen in adenomas, complex adenomas, benign mixed tumors, ductular carcinomas, and one myoepithelioma-like tumor. Additionally, cytokeratin positive cells were scattered interstitially in one single adenoma, most complex adenomas, some benign mixed tumors, complex carcinomas, and in the malignant mixed tumors. All stromal cells stained positively for vimentin. The fibrosarcomas were positive only for vimentin, while the following expressed both desmin and cytokeratin: epithelial-like cells in one adenoma, three complex adenomas, the myoepithelioma-like tumor, the single comedo carcinoma, two complex carcinomas, the single lobular carcinoma, one malignant mixed tumor, and three osteosarcomas. Epithelial-like cells in one adenoma, six complex adenomas, two benign mixed tumors, two complex carcinomas, the lobular carcinoma, and the malignant schwannoma stained for neurofilaments. Three tumors, one adenoma, one complex adenoma, and the lobular carcinoma expressed both desmin and neurofilaments in addition to cytokeratin and vimentin. The results show the expression of different types of intermediate filaments and indicate that there might be a stem cell origin in most of the canine mammary tumors.

Adenoma↗

PubMed1998

Intra-abdominal follicular dendritic cell tumour: a rare tumour in need of recognition.

AIMS: Neoplasms of follicular dendritic cells are uncommon and the majority of them occur in lymph nodes. Rarely, they may occur inside the abdominal cavity. We describe two examples of intra-abdominal follicular dendritic cell (FDC) tumour. One involved the liver and the other involved the ampulla of Vater. Our aims are to complement the current understanding on this disease and to alert histopathologists and clinicians to this rare entity. MATERIALS AND RESULTS: The clinical and radiological findings of the two cases of intra-abdominal follicular dendritic cell tumours were reviewed. The resected specimens were examined macroscopically and microscopically. Immunohistochemical studies, ultrastructural examination and in situ hybridization for Epstein-Barr virus were also performed. Both tumours could not be accurately diagnosed before pathological examination of the resected specimens. The soft to slightly firm consistency of the tumours resembled that of fixed brain tissue, and was distinctly different from hepatocellular carcinoma or pancreatic carcinoma. The fascicular arrangement of syncytial plump to spindle cells in a background of mixed inflammatory cells was the initial clue to the diagnosis, which was confirmed by the immunoreactivity of the tumour cells to follicular dendritic cell markers (CD21 and CD35), and by the demonstration of focal intercellular desmosome-like junctions between the complex cytoplasmic processes of the tumour cells. The tumour cells in the liver tumour also showed presence of Epstein-Barr virus on in situ hybridization study. CONCLUSIONS: Awareness of the entity and the ability to recognize this tumour by histopathologists are emphasized because the tumour closely mimics a wide variety of other tumours and tumour-like lesions. Similar to the other reported FDC tumours of the liver, our case of hepatic follicular dendritic cell tumour is also positive for Epstein-Barr virus, suggesting that the virus may play a role in its pathogenesis.

Adult↗

PubMed1994

Ex vivo evaluation of pidotimod activity on cell-mediated immunity.

The activity of pidotimod ((R)-3-[(S)-(5-oxo2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) on immunological parameters was evaluated in a double-blind trial, involving two Research Centres. 16 patients with a primary or metastatic neoplasm, 16 elderly patients under immunodeficiency conditions and 11 healthy volunteers were enrolled in the present study. The patients, randomized within each centre, were assigned to one of the following treatments lasting 15 days: one vial i.m. of pidotimod 50 mg, 100 mg, 200 mg twice a day, respectively; one vial i.m. of physiological saline twice a day. The lymphocyte PHA-stimulation test evidenced a significant variability due to the different treatment groups (p = 0.004). The analysis of the stimulation index (SI), computed from the mean c.p.m. before and after PHA-stimulation, showed a significant difference, dose-independent, between saline and active treatment (p = 0.002). The SI analysis, on the basis of the data of the allogenic stimulation test (mixed lymphocyte culture), confirmed the difference between saline and active treatment (p = 0.05) with a significant linear component in the time-effect curve (p = 0.001) but not in the dose-effect curve. A 12% increase in CD 3 lymphocytes compartment was observed with pidotimod 400 mg/day. The drug was well tolerated by all the patients included in the study.

Adjuvants, Immunologic↗

PubMed1993

Induction of tumor-cell lysis by bi-specific antibody recognizing ganglioside GD2 and T-cell antigen CD3.

Human tumor cells expressing ganglioside GD2 were lysed by various effector populations targeted with an anti-CD3-anti-GD2 bi-specific antibody (BAb CD3 x GD2). This antibody-heteroconjugate was prepared by chemically cross-linking the OKT-3 monoclonal antibody (MAb) reactive with CD3 antigen on T lymphocytes with the ganglioside MAb ME 361, which binds preferentially to the tumor-associated ganglioside GD2. The specificity of target-cell lysis by the cytotoxic T cells (CTL) was mediated by the specificity of the targeting antibody: GD2-negative cells were not lysed in the presence of the CD3 x GD2 BAb. A dose-dependent response was observed in a range of 10 to 10,000 ng/ml. In contrast, 2 other BAbs recognizing the tumor-associated antigens EGF-R and TKB-2 had greater potency to mediate tumor-cell lysis than the GD2 x CD3 BAb. Peripheral-blood cells (PBL) stimulated with OKT-3 MAb or with irradiated tumor cells in a mixed lymphocyte culture (MLTC) could be induced to lyse GD2-positive tumor cells in the presence of CD3 x GD2 BAb. The tumor-cell lysis could be mediated by autologous or allogeneic effector cells. NK cells had no influence on the BAb-induced cytotoxicity.

Antibodies↗