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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Immunological reviews 145 (1995), S. 0 
    ISSN: 1600-065X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé L'importance relative des facteurs pronostiques dans les cancers papillaires et folliculaires de la thyroïde ont été étudiés chez 113 patients selon le modèle de Cox. Voici les facteurs de pronostic étudiés: histologie, degré de différentiation, extension extrathyroïdienne, envahissement ganglionnaire, présence de métastase à distance au moment du diagnostic, contenu nucléaire en ADN, âge au moment du diagnostic, et sexe. Le contenu d'ADN nucléaire était mesuré dans les tumeurs primitives par la cytométrie de flux. La thyroïdectomie totale suivie d'I 131 était le traitement standard. Les résultats montraient que le contenu nucléaire en ADN était en corrélation significative avec le type histologique et le degré de malignité dans les cancers papillaires. La présence de métastases à distance était de loin le facteur pronostique le plus important. Dans le groupe de patients sans métastases (n=91), la présence de polyploïdie (c'est-à-dire 2 chaînes aberrantes ou plus) était le facteur pronostique significatif pour la survie globale. Pour la survie sans maladie, la polyploïdie venait après le facteur âge. Dans le groupe présentant des métastases à distance (n=22), tous les patients avec tumeurs polyploïdes sont morts pour huit patients de ceux qui avaient des tumeurs à ploïdie différente. Mais le petit nombre de patients de ce groupe interdit de considérer ces résultats comme significatifs. Cette étude démontre que le contenu nucléaire en ADN est un facteur pronostique chez les patients ayant un cancer papillaire et folliculaire sans métastases au moment du diagnostic.
    Abstract: Resumen La importancia relativa de los factores de pronóstico en el cancer papilar y folicular de la glándula tiroides fue estudiada en 113 pacientes utilizando el modelo de riesgos proporcionales de Cox. Los factores de pronóstico analizados fueron: histologia, grado tumoral, crecimiento extratiroideo, extension ganglionar, metastasis distantes en el momento del diagnóstico, contenido nuclear de DNA, edad en el momento del diagnóstico, y sexo. El contenido nuclear de DNA fue determinado en tumores primarios mediante citometn'a de flujo. El tratamiento estandar fue la tiroidectomía total y la ablación postoperatoria con131I. Los resultados muestran que el contenido nuclear de DNA se correlaciona en forma significativa con el tipo histológico y en el cancer papilar también con el grado tumoral. La presencia de metastasis distantes en el momento del diagnóstico es, muy ampliamente, el más importante factor de pronóstico. En el grupo de pacientes libre de metastasis distantes (n=91), la multiploidia (i.e., presencia de 2 o más lineas primitivas aberrantes) aparece como el único factor de significatión en cuanto a supervivencia global. Respecto a supervivencia libre de enfermedad la multiploidia aparece como segundo factor, después de la edad. En el grupo de pacientes con metástasis distantes (n=22) todos los 6 pacientes con tumores multiploides murieron, en comparación con 8 (50%) de 16 de aquellos con tumores con cualquier otro tipo de ploidia. Sinembargo, el pequeno número que constituye este grupo impide derivar resultados de signification. El presente estudio demuestra que el contenido nuclear de DNA es un factor pronóstico en pacientes con cancer tiroideo papilar y folicular libres de metastasis distantes.
    Notes: Abstract The relative importance of prognostic factors in papillary and follicular thyroid cancer was studied in 113 patients using Cox's proportional hazards model. Prognostic factors studied were: histology, tumor grade, extrathyroidal growth, nodal involvement, distant métastases at diagnosis, nuclear DNA content, age at diagnosis, and sex. Nuclear DNA content was measured in primary tumors by flow cytometry. Total thyroidectomy and postoperative131I ablation was the standard treatment. The results showed that nuclear DNA content correlated significantly with histologic type and, in papillary cancer, also with tumor grade. The presence of distant metastases at diagnosis was, by far, the most important prognostic factor. In the patient group without distant metastases (n=91), multiploidy (i.e., presence of 2 or more aberrant stemlines) was the only significant prognostic factor for overall survival. With respect to diseasefree survival, multiploidy was second only to the age factor. In the patient group with distant métastases (n=22), all 6 patients with multiploid tumors died compared to 8 (50%) of 16 of those with other ploidy tumors. However, the small number in this group precluded significant results. The present study demonstrates that nuclear DNA content is a prognostic factor in those patients with papillary and follicular thyroid cancer without distant metastases at diagnosis.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0851
    Keywords: Lymphokine-activated killer activity ; 2-Mercaptoethanol ; Indomethacin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The role of 2-mercaptoethanol and indomethacin in the induction of lymphokine-activated killer (LAK) activity by interleukin-2 (IL-2) in rat splenocyte cultures was investigated. Spleens from 4-month-old male rats of five different strains were tested. Splenocytes were cultured for 3–5 days in the presence of IL-2 (1000 U/ml) and LAK activity was assessed by 4-h51Cr release assays with P815 and YAC-1 cells as targets. LAK activity could be induced by IL-2 in splenocytes from all rat strains, but only when 2-mercaptoethanol was present in the culture medium. Optimal LAK activity was induced when the 2-mercaptoethanol concentration in splenocyte cultures was at least 5 µM. Different rat strains showed differences in levels of in vitro induction of LAK activity. In the presence of 2-mercaptoethanol the level of LAK activity induced by IL-2 was high in BN and Lewis rats, intermediate in Wistar and Wag rats, and low in DZB rats. In the absence of 2-mercaptoethanol no or minimal LAK activity was induced. Furthermore we observed that addition of 50 µm indomethacin to the culture medium in the presence of 2-mercaptoethanol augmented the induction of LAK activity to some extent. In the absence of 2-mercaptoethanol, addition of indomethacin resulted only in low levels or no induction of LAK activity. We conclude that for optimal induction of LAK activity by IL-2 in rat splenocyte cultures 2-mercaptoethanol is essential, while indomethacin can only marginally further improve this induction.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0851
    Keywords: Bispecific monoclonal antibody ; Lymphokine-activated killer cell ; Rat ; CD8
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In vivo targeting of lymphokine-activated killer (LAK) cells to tumour deposits by bispecific monoclonal antibodies (bimAb) may be a way to improve adoptive immunotherapy. We developed a bimAb against adherent LAK (ALAK) cells and colon tumour CC531 in Wag rats. The bimAb was produced by somatic hybridization of two mouse hybridomas, one producing monoclonal antibodies (mAb) against CD8 (IgG2b, OX8), and the other producing mAb against a CC531-associated antigen (IgG1, CC52). A bimAb-producing clone was selected by an enzyme-linked immunosorbent assay with CC531 tumour cells. BimAb were purified from ascitic fluid by protein A affinity chromatography. Each of five pooled peak fractions was analysed by flow cytometry for the presence of bimAb. Most bimAb were found in a fraction that was eluted at pH 4.5 from protein A. FPLC analysis of this fraction revealed that no parental antibodies were present. The OX8 × CC52 bimAb greatly increased conjugate formation in vitro between ALAK cells and CC531. Results of51Cr-release assays with CC531 as target cells and ALAK cells as effector cells were not significantly different in the presence or in the absence of the bimAb. The methods we used here, a cell enzyme-linked immunosorbent assay and flow cytometry, are simple methods for development and purification of a bimAb when a functional selection method is not a priori available. The OX8 × CC52 bimAb we developed this way may increase in vivo tumour targeting of ALAK cells and thus augment antitumour effect in vivo.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous experiments in a syngeneic rat liver tumor model using the colon adenocarcinoma CC531 demonstrated that injection of interleukin-2 (IL-2) induced significant antitumor responses. Furthermore, it was found that this treatment strategy was accompanied by an increase in the number of natural killer (NK) cells in and around the tumor. In the present study, the role of endogenous NK cells in IL-2-mediated antitumor responses was further elucidated by depleting tumor-bearing rats of NK cells, using the anti-CD161A mouse IgG1 antibody 3.2.3. Rats were depleted either after or prior to tumor induction and subsequently treated with IL-2. The results demonstrated that depletion of NK cells in tumor-bearing rats did not influence IL-2-induced antitumor effects. In addition, injection of IL-2 in NK-cell-depleted rats induced repopulation of NK cells in the peripheral blood from 3 days on and further after the last injection with IL-2. Therefore, the possibility cannot be excluded that de novo recruited NK cells play a role in attaining IL-2 mediated antitumor effects, but NK cells, which were present before or during the start of IL-2 therapy, were not relevant.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0851
    Keywords: Lymphokine-activated killer activity ; Interleukin-2 ; 2-Mercaptoethanol ; Macrophages/monocytes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present study we investigated the inhibition of interleukin-2(IL-2)-induced lymphokine-activated killer (LAK) activity in rat splenocyte cultures in relation to the presence of 2-mercaptoethanol and macrophages/monocytes. The presence of 2-mercaptoethanol is necessary for induction of LAK activity in rat splenocyte cultures. Removal of macrophages/monocytes from rat splenocytes by plastic or nylon-wool adherence, or iron ingestion resulted in LAK induction by IL-2 in the absence of 2-mercaptoethanol. The effect of macrophages/monocytes on LAK activity was also studied in transwell co-cultures. In the absence of 2-mercaptoethanol, the induction of LAK activity was very low in macrophage/monocyte-depleted splenocytes with macrophages/monocytes in the upper compartment of a transwell culture. In contrast, in the presence of 2-mercaptoethanol a high level of LAK activity was induced in these transwell cultures, showing that 2-mercaptoethanol abolished the LAK-inhibiting capacity of macrophages/monocytes. In addition, established LAK activity was strongly inhibited when, after LAK induction, splenocytes were cultured with supernatant of unfractionated splenocytes, which were cultured with IL-2 but in the absence of 2-mercaptoethanol. Addition of 2-mercaptoethanol abrogated the inhibiting effect of the supernatant completely. These experiments demonstrate that rat macrophages/monocytes produce 2-mercaptoethanolsensitive soluble LAK-inhibiting factors. Ultrafiltration of conditioned culture medium of macrophages/monocytes revealed the presence of LAK-inhibiting factors larger than 10 kDa. We concluded that 2-mercaptoethanol-sensitive soluble factors produced by macrophages/monocytes determine the level of LAK induction in rat splenocyte cultures.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0851
    Keywords: Key words: Lymphokine-activated killer activity – Interleukin-2 – 2-Mercaptoethanol – Macrophages/monocytes – Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. In the present study we investigated the inhibition of interleukin-2(IL-2)-induced lymphokine-activated killer (LAK) activity in rat splenocyte cultures in relation to the presence of 2-mercaptoethanol and macrophages/monocytes. The presence of 2-mercaptoethanol is necessary for induction of LAK activity in rat splenocyte cultures. Removal of macrophages/monocytes from rat splenocytes by plastic or nylon-wool adherence, or iron ingestion resulted in LAK induction by IL-2 in the absence of 2-mercaptoethanol. The effect of macrophages/monocytes on LAK activity was also studied in transwell co-cultures. In the absence of 2-mercaptoethanol, the induction of LAK activity was very low in macrophage/monocyte-depleted splenocytes with macrophages/monocytes in the upper compartment of a transwell culture. In contrast, in the presence of 2-mercaptoethanol a high level of LAK activity was induced in these transwell cultures, showing that 2-mercaptoethanol abolished the LAK-inhibiting capacity of macrophages/monocytes. In addition, established LAK activity was strongly inhibited when, after LAK induction, splenocytes were cultured with supernatant of unfractionated splenocytes, which were cultured with IL-2 but in the absence of 2-mercaptoethanol. Addition of 2-mercaptoethanol abrogated the inhibiting effect of the supernatant completely. These experiments demonstrate that rat macrophages/monocytes produce 2-mercaptoethanol-sensitive soluble LAK-inhibiting factors. Ultrafiltration of conditioned culture medium of macrophages/monocytes revealed the presence of LAK-inhibiting factors larger than 10 kDa. We concluded that 2-mercaptoethanol-sensitive soluble factors produced by macrophages/monocytes determine the level of LAK induction in rat splenocyte cultures.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-7276
    Keywords: colon cancer ; immunotherapy ; matrix proteins ; metastasis ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The colon adenocarcinoma cell line CC531 was adopted as a model for immunotherapeutical treatment of experimental colorectal metastases in a syngeneic rat model. We studied the presence and localization of T and natural killer cells, vessels and matrix proteins in in vivo growing CC531 tumours by immunohistochemistry. CC531 tumours were induced either in the lungs by injecting CC531 tumour cells into a tail vein or in the liver by injection of CC531 tumour cells under the liver capsule or into a mesenteric vein. All 3 tumour types were composed of islets of tightly apposed tumour cells surrounded by abundantly present tumour-stroma which contained tumour vessels and matrix proteins. Some of these matrix proteins, especially laminin and collagen IV formed a basal membrane-like structure around the tumour nodules. This structure was most pronounced in mesenteric vein-induced liver tumours and less prominent in subcapsular-induced liver tumours and tail vein-induced lung tumours. Tumour-infiltrating lymphocytes of both T and natural killer cell origin were found in the tumours, but predominantly in the tumour stroma, separated from the islets of tumour cells by the basal membrane-like structure. We hypothesize that the matrix proteins of these tumours play an ambivalent role: they may provide a substratum for migration of effector cells into the tumour stroma but may also provide a barrier preventing direct contact between tumour target cells and immune effector cells.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-7276
    Keywords: colon tumour ; monoclonal antibody ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this paper we describe 4 new monoclonal antibodies to be applied in rat models for cancer. The monoclonal antibodies were obtained by immunizing Balb/c mice with CC531 rat colon adenocarcinoma cells. Hybridomas were produced and 4 were selected for their reactivity with CC531 in vitro (MG1, 2, 3 and 4). All 4 antibodies recognized other rat tumour cell lines and showed limited cross-reactivity with normal rat tissues. Intraperitoneally injected MG1, 2 and 4 homed to in vivo growing, artificially induced CC531 liver metastases. In these in vivo experiments, limited cross-reactivity with normal rat tissues, predominantly of the gastro-intestinal tract, was found. MG4 was found to enhance lysis of CC531 tumour cells mediated by IL-2 activated, cultured natural killer cells. These antibodies are potentially useful for antibody-based laboratory techniques and for investigation of antibody-based immunotherapy of cancer in a rat model.
    Type of Medium: Electronic Resource
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