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1.
Weisong Xu Edwin de Zoeten Victoria Carr-Brendel E. P. Cohen 《Cancer immunology, immunotherapy : CII》1997,45(5):217-224
Tumor-associated T cell epitopes are recognized by T cells in the context of determinants specified by class I loci. Since
the rejection of foreign histocompatibility antigens is known to enhance tumor immunity, immunization with a cellular vaccine
that combined the expression of both syngeneic and allogeneic class I determinants could have important immunological advantages
over a vaccine that expressed either syngeneic or allogeneic determinants alone. To investigate this question in a mouse melanoma
model system, we tested the immunotherapeutic properties of B16 melanoma × LM fibroblast hybrid cells in C57BL/6J mice with
melanoma. Like C57BL/6J mice, B16 cells expressed H-2Kb class I determinants and (antibody-defined) melanoma-associated antigens. LM cells, of C3H mouse origin, formed H-2Kk determinants along with B7.1, a co-stimulatory molecule that can activate T cells. The B16 × LM hybrid cells co-expressed
H-2Kb and H-2Kk class I determinants, B7.1 and the melanoma-associated antigens. C57BL/6J mice with melanoma, immunized with the semi-allogeneic
hybrid cells, developed CD8-mediated melanoma immunity and survived significantly (P<0.005) longer than mice with melanoma
immunized with a mixture of the parental cell types. The failure of melanoma immunity to develop in mice injected with the
mixture of parental cells indicated that co-expression of the immunogenic determinants by the same cellular immunogen was
necessary for an optimum immunotherapeutic effect. Augmented immunity to melanoma in mice immunized with the semi-allogeneic
hybrid cells points toward an analogous form of therapy for patients with melanoma.
Received: 19 May 1997 / Accepted: 23 July 1997 相似文献
2.
Cecilia Bergenwald Gunilla Westermark B. Sander 《Cancer immunology, immunotherapy : CII》1997,44(6):335-340
Tumor necrosis factor α (TNFα) is a cytokine, produced by lymphocytes and monocytes, with cytotoxic activity against some
but not all tumor cell lines. Resistance to the cytolytic effects of TNFα has been reported in cell lines with autocrine TNFα
production. The purpose of this study was to investigate whether human primary malignant melanoma and tumor infiltrating lymphocytes
produce TNFα in vivo. Optimal conditions for in situ hybridization for TNFα mRNA in paraffin-embedded tissue were established.
Analysis of 13 primary malignant melanomas and 3 metastatic lesions with different degrees of immunohistochemical TNFα positivity
demonstrated that, in some tumors, both melanoma cells and leukocytes contained TNFα mRNA and protein. These findings demonstrate
variable production of TNFα in primary and metastatic melanoma in vivo.The previously described resistance to TNFα cytolytic
activity may, therefore, be clinically important.
Received: 18 December 1996 / Accepted: 12 June 1997 相似文献
3.
Toshihiro Fujimoto Michael A. O’Donnell Akos Szilvasi H. Yang R. B. Duda 《Cancer immunology, immunotherapy : CII》1996,42(5):280-284
Although immunotherapy with bacillus Calmette Guérin (BCG) is an established adjuvant treatment for malignant melanoma, the
mechanism of its role in this process is unclear. To investigate the possible contribution of tumor-inhibitory cytokines induced
by BCG, B16F10 melanoma cell growth in culture was assessed in response to purified cytokines and conditioned media of BCG-stimulated
splenocytes. Interferon-γ (IFNγ) was the most potent single agent (IC50≈50 pg/ml). Tumor necrosis factor α was substantially weaker (IC50>10 ng/ml) but provided synergy with IFNγ. None of the other
cytokines such as interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-12, or granulocyte/macrophage-colony-stimulating factor had
direct antitumor activity against B16F10 melanoma cells. However, when IL-2 and/or GM-CSF were combined with BCG either by
exogenous addition or through endogenous production by novel cytokine-secreting recombinant BCG (rBCG), a substantial increase
in INFγ production by splenocytes was observed. Antitumor activity of this conditioned medium directly correlated with IFNγ
concentration and was completely blocked by neutralizing antibody to IFNγ. These results suggest that BCG may exert part of
its antitumor action on melanoma through the induction of IFNγ, which can be greatly enhanced through the concomitant addition
of IL-2 and/or GM-CSF. Furthermore, by utilizing rBCG that secrete these cytokines, it may be possible to potentiate the antitumor
effect of BCG directly at the site of BCG inoculation.
Received: 29 January 1996 / Accepted: 9 April 1996 相似文献
4.
5.
S. Lausson B. Fournes C. Borrel G. Milhaud F. Treilhou-Lahille 《Cancer immunology, immunotherapy : CII》1996,43(2):116-123
The existence of inherited aggressive forms of medullary thyroid carcinoma (MTC), and their resistance to all classical therapies,
make it a prime candidate for adoptive immunotherapy. As a prelude to a vaccine for the protection of family members at risk
of developing the disease, we investigated the immunological antitumour response provoked by the 6/23 rMTC cell line, compared
to that of the same cells engineered to secrete interleukin-2 (rMTC-IL2), in an animal model of familial human MTC, the inbred
strain of Wag/Rij rats. The rMTC cells developed a tumour that invaded the whole neck 15 days after orthotopic injection (into
the thyroid), while the rMTC-IL2 cells were progressively rejected. Co-injection of rMTC-IL2 with the parental cells induced
the rejection of the rMTC transplants. When injected, both tumoral cell types showed a similar positive immunoreaction with
anti-MHC class I (major histocompatibility complex class I) antibodies. They both recruited natural killer cells and eosinophils
at the site of injection. In addition, CD8+ T lymphocytes infiltrated the rMTC-IL2 cells, and eosinophil recruitment was amplified. Neutrophils, macrophages and CD4+ T lymphocytes were scarce. Our results suggest that the CD8+ T lymphocytes are implicated in the antitumour reaction elicited by the Il-2-transfected cells. As these effectors are known
to induce a specific immunological response, including memory, such a protocol should be tested as a vaccine on the young
population genetically at risk of developing a MTC.
Received: 18 December 1995 / Accepted: 21 August 1996 相似文献
6.
Ying Chang Laila Al-Alwan Sama Alshakfa Severine Audusseau Andrea Karen Mogas Fazila Chouiali Parameswaran Nair Carolyn J Baglole Qutayba Hamid David H Eidelman 《Respiratory research》2014,15(1)
Background
Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder marked by relative resistance to steroids. The IL-17 superfamily, which mediates cross-talk between the adaptive and innate immune systems, has been associated with diminished responses to steroids. Increasing evidence supports elevated IL-17 expression in the lung of COPD subjects. However, whether cells of the immune system (systemic) and/or local lung cells are contributing to the elevated IL-17 remains unclear. To address this issue, we utilized a human parenchymal lung tissue explant culture system with cigarette smoke exposure to investigate the expression of IL-17 and the mechanisms involved.Methods
Parenchymal lung tissue removed from 10 non-COPD and 8 COPD patients was sectioned and cultured with different concentrations of cigarette smoke extract (CSE) for 3 or 6 hours. Tissue viability was evaluated by LDH (lactate dehydrogenase) in culture supernatants. Western blot and real-time PCR were performed to evaluate IL-17A/F expression. To investigate the mechanisms, pharmacological inhibitors for MAPK p38, ERK1/2, NF-κB and PI3K pathways were added into the culture media.Results
No tissue damage was observed after the cigarette smoke exposure for 3 h or 6 h compared with the control media. At the protein level, the expression of both IL-17A (2.4 ± 0.6 fold) and IL-17 F (3.7 ± 0.7 fold) in the tissue from non-COPD subjects was significantly increased by 5% of CSE at 3 h. For COPD subjects, IL-17A/F expression were significantly increased only at 6 h with 10% of CSE (IL-17A: 4.2 ± 0.8 fold; IL-17 F: 3.3 ± 0.8 fold). The increased expression of IL-17A/F is also regulated at the mRNA level. The inhibitors for NF-κB and PI3K pathways significantly inhibited CSE-induced IL-17A/F expression from lung tissue of non-COPD subjects.Conclusions
We found the evidence that the expression of both IL-17A and IL-17 F is increased by the cigarette smoke exposure in explants from both non-COPD and COPD subjects, supporting that local lung cells contribute IL-17 production. The elevated IL-17A/F expression is dependent on NF-κB and PI3K pathways. These observations add to the growing evidence which suggests that Th17 cytokines play a significant role in COPD. 相似文献7.
K. A. O. Ellem Michael G. E. O’Rourke Gregory R. Johnson Gordon Parry Ihor S. Misko Christopher W. Schmidt Peter G. Parsons Scott R. Burrows Simone Cross Andrew Fell Chung-Leung Li John R. Bell Philip J. Dubois Denis J. Moss Michael F. Good Anne Kelso Lawrence K. Cohen Glenn Dranoff Richard C. Mulligan 《Cancer immunology, immunotherapy : CII》1997,44(1):10-20
The first use of granulocyte/macrophage-colony-stimulating-factor-transduced, lethally irradiated, autologous melanoma cells
as a therapeutic vaccine in a patient with rapidly progressive, widely disseminated malignant melanoma resulted in the generation
of a novel antitumour immune response associated with partial, albeit temporary, clinical benefit. An initially negative reaction
to non-transduced, autologous melanoma cells was converted to a delayed-type hypersensitivity (DTH) reaction of increasing
magnitude following successive vaccinations. While intradermal vaccine sites showed prominent dendritic cell accrual, DTH
sites revealed a striking influx of eosinophils in addition to activated/memory T lymphocytes and macrophages, recalling the
histology of challenge tumour cell rejection in immune mice. Cytotoxic T lymphocytes (CTL) reactive with autologous melanoma
cells were detectable at high frequency after vaccination, not only in limiting-dilution analysis, but also in bulk culture
without added cytokines. Clonal analysis of CTL showed a conversion from a purely CD8+ response to a high proportion of CD4+ clones following vaccination. A prominent acute-phase response manifested by a five- to tenfold increase in C-reactive protein
was observed, as was a systemic eosinophilia. Vaccination resulted in the regression of axillary lymphatic metastases, stabilisation
of pulmonary metastases, and a dramatic, reversible increase in cerebral oedema associated with multiple central nervous system
metastases; however, lesions in the adrenal glands, pancreas and spleen proved refractory. The antitumour effects and immune
response were not detectable 2 months following the last vaccination. Irradiation of the extensive cerebral metastases resulted
in rapid deterioration and death of the patient.
Received: 20 September 1996 / Accepted: 5 December 1996 相似文献
8.
Arabella Mazzocchi Cecilia Melani Licia Rivoltini Chiara Castelli Michele Del Vecchio Claudia Lombardo Mario P. Colombo Giorgio Parmiani 《Cancer immunology, immunotherapy : CII》2001,50(4):199-211
In order to construct an immunogenic cellular vaccine, we transduced three HLA-A*0201 human melanoma lines, selected for
expression of classes I and II HLA, adhesion molecules and the T cell-defined melanoma antigens Melan/MART-1, gp100 and tyrosinase,
with both interleukin-2 (IL-2) and B7-1 genes by the use of a polycistronic retroviral vector. The lines were selected to
share only the HLA-A*0201 allele to avoid generation of strong alloreactivity in case of their multiple in vivo use in HLA-A*0201
+ patients. Phenotypic and functional analysis of B7-1-IL2 transduced melanoma lines in comparison with B7-1 transduced and/or
parental untransduced counterparts were then carried out. Tumor cells expressing either B7-1 or both genes did not change
their original antigenic profile. From a functional point of view, expression of both genes in melanoma lines: (1) improved
the response of anti-melanoma cytotoxic T lymphocytes (CTL) over singly transduced or untransduced melanoma cells when subthreshold
levels of MHC-peptide complexes were expressed by melanoma cells; (2) conferred a distinct advantage in the ability to stimulate
cytotoxicity and interferon-γ release by autologous and/or HLA-A*0201-compatible allogeneic lymphocytes; (3) allowed the generation
of a high number of specific CTL by in vitro stimulation of lymphocytes of HLA-A*0201-melanoma patients. Thus, B7-IL2 gene-transduced
melanoma lines appear to display a high immunogenicity and could be used as vaccine in melanoma patients.
Received: 17 August 2000 / Accepted: 1 February 2001 相似文献
9.
10.
The current-voltage (I/V) profiles of Ventricaria (formerly Valonia) membranes were measured at a range of external potassium concentrations, [K+]
o
, from 0.1 to 100 mm. The conductance-voltage (G/V) characteristics were computed to facilitate better resolution of the profile change with time after exposure to different
[K+]
o
. The resistance-voltage (R/V) characteristics were computed to attempt resolution of plasmalemma and tonoplast. Four basic electrophysiological stages
emerged: (1) Uniform low resistance between −60 and +60 mV after the cell impalement. (2) High resistance between +50 and
+150 for [K+]
o
from 0.1 to 1.0 mm and hypotonic media. (3) High resistance between −150 and −20 mV for [K+]
o
of 10 mm (close to natural seawater) and hypertonic media. (4) High resistance between −150 and +170 mV at [K+]
o
of 100 mm.
The changes between these states were slow, requiring minutes to hours and sometimes exhibiting spontaneous oscillations of
the membrane p.d. (potential difference). Our analysis of the I/V data supports a previous hypothesis, that Ventricaria tonoplast is the more resistive membrane containing a pump, which transports K+ into the vacuole to regulate turgor. We associate state (1) with the plasmalemma conductance being dominant and the K+ pump at the tonoplast short-circuited probably by a K+ channel, state (2) with the K+ pump ``off' or short-circuited at p.d.s more negative than +50 mV, state (3) with the K+ pump ``on,' and state (4) with the pump dominant, but affected by high K+. A model for the Ventricaria membrane system is proposed.
Received: 5 November 1998/Revised: 11 May 1999 相似文献
11.
K. Ushijima H. Sassa R. Tao H. Yamane A. M. Dandekar T. M. Gradziel H. Hirano 《Molecular & general genetics : MGG》1998,260(2-3):261-268
cDNAs encoding three S-RNases of almond (Prunus dulcis), which belongs to the family Rosaceae, were cloned and sequenced. The comparison of amino acid sequences between the S-RNases
of almond and those of other rosaceous species showed that the amino acid sequences of the rosaceous S-RNases are highly divergent,
and intra-subfamilial similarities are higher than inter-subfamilial similarities. Twelve amino acid sequences of the rosaceous
S-RNases were aligned to characterize their primary structural features. In spite of␣their high level of diversification,
the rosaceous S-RNases were found to have five conserved regions, C1, C2, C3, C5, and RC4 which is Rosaceae-specific conserved
region. Many variable sites fall into one region, named RHV. RHV is located at a similar position to that of the hypervariable
region a (HVa) of the solanaceous S-RNases, and is assumed to be involved in recognizing S-specificity of pollen. On the other hand, the region corresponding to another solanaceous hypervariable region (HVb) was
not variable in the rosaceous S-RNases. In the phylogenetic tree of the T2/S type RNase, the rosaceous S-RNase fall into two
subfamily-specific groups (Amygdaloideae and Maloideae). The results of sequence comparisons and phylogenetic analysis imply
that the present S-RNases of Rosaceae have diverged again relatively recently, after the divergence of subfamilies.
Received: 28 May 1998 / Accepted: 13 August 1998 相似文献
12.
Sowmya Raghavan Pradeep K. Burma Samir K. Brahmachari 《Journal of molecular evolution》1997,45(5):485-498
The complete genome of the baker's yeast S. cerevisiae was analyzed for the presence of polypurine/polypyrimidine (poly[pu/py]) repeats and their occurrences were classified on
the basis of their location within and outside open reading frames (ORFs). The analysis reveals that such sequence motifs
are present abundantly both in coding as well as noncoding regions. Clear positional preferences are seen when these tracts
occur in noncoding regions. These motifs appear to occur predominantly at a unit nucleosomal length both upstream and downstream
of ORFs. Moreover, there is a biased distribution of polypurines in the coding strands when these motifs occur within open
reading frames. The significance of the biased distribution is discussed with reference to the occurrence of these motifs
in other known mRNA sequences and expressed sequence tags. A model for cis regulation of gene expression is proposed based on the ability of these motifs to form an intermolecular triple helix structure
when present within the coding region and/or to modulate nucleosome positioning via enhanced histone affinity when present
outside coding regions.
Received: 14 November 1996 / Accepted: 7 May 1997 相似文献
13.
Sibling neurons in the embryonic central nervous system (CNS) of Drosophila can adopt distinct states as judged by gene expression and axon projection. In the NB4-2 lineage, two even-skipped (eve)-expressing sibling neuronal cells, RP2 and RP2sib, are formed in each hemineuromere. Throughout embryogenesis, only RP2, but not RP2sib, maintains eve expression. In this report, we describe a P-element induced mutation that alters the expression pattern of EVE in RP2 motoneurons in the Drosophila embryonic CNS. The mutation was mapped to a Drosophila homolog of human AF10/AF17 leukemia fusion genes (alf), and therefore named Dalf. Like its human counterparts, Dalf encodes a zinc finger/leucine zipper nuclear protein that is widely expressed in embryonic and larval tissues including neurons and glia. In Dalf mutant embryos, the RP2 motoneuron no longer maintains EVE expression. The effect of the Dalf mutation on EVE expression is RP2-specific and does not affect other characteristics of the RP2 motoneuron. In addition to the embryonic phenotype, Dalf mutant larvae are retarded in their growth and this defect can be rescued by the ectopic expression of a Dalf transgene under the control of a neuronal GAL4 driver. This indicates a requirement for Dalf function in the nervous system for maintaining gene expression and the facilitation of normal growth. 相似文献
14.
15.
Sibling neurons in the embryonic central nervous system (CNS) of Drosophila can adopt distinct states as judged by gene expression and axon projection. In the NB4-2 lineage, two even-skipped (eve)-expressing sibling neuronal cells, RP2 and RP2sib, are formed in each hemineuromere. Throughout embryogenesis, only RP2, but not RP2sib, maintains eve expression. In this report, we describe a P-element induced mutation that alters the expression pattern of EVE in RP2 motoneurons in the Drosophila embryonic CNS. The mutation was mapped to a Drosophila homolog of human AF10/AF17 leukemia fusion genes (alf), and therefore named Dalf. Like its human counterparts, Dalf encodes a zinc finger/leucine zipper nuclear protein that is widely expressed in embryonic and larval tissues including neurons and glia. In Dalf mutant embryos, the RP2 motoneuron no longer maintains EVE expression. The effect of the Dalf mutation on EVE expression is RP2-specific and does not affect other characteristics of the RP2 motoneuron. In addition to the embryonic phenotype, Dalf mutant larvae are retarded in their growth and this defect can be rescued by the ectopic expression of a Dalf transgene under the control of a neuronal GAL4 driver. This indicates a requirement for Dalf function in the nervous system for maintaining gene expression and the facilitation of normal growth. 相似文献
16.
Chiu CH Amemiya CT Carr JL Bhargava J Hwang JK Shashikant CS Ruddle FH Wagner GP 《Development genes and evolution》2000,210(2):105-109
The identification of cis-sequences responsible for spatiotemporal patterns of gene expression often requires the functional analysis of large genomic
regions. In this study a 100-kb zebrafish Hoxa-11b-lacZ reporter gene was constructed and expressed in transgenic mice. PAC clone 10-O19, containing a portion of the zebrafish HoxA-b
cluster, was captured into the yeast-bacterial shuttle vector, pPAC-ResQ, by recombinogenic targeting. A lacZ reporter gene was then inserted in-frame into exon 1 of the zfHoxa-11b locus by a second round of recombinogenic targeting. Expression of the zfHoxa-11b-lacZ reporter gene in 10.5 d.p.f. transgenic mouse embryos was observed only in the posterior portion of the A-P axis, in the paraxial mesoderm, neural tube,
and somites. These findings demonstrate the utility of recombinogenic targeting for the modification and expression of large
inserts captured from P1/PAC clones.
Received: 22 June 1999 / Accepted: 1 September 1999 相似文献
17.
18.
19.
The embryonic development of amphioxus (cephalochordates) has much in common with that of vertebrates, suggesting a close
phylogenetic relationship between the two chordate groups. To gain insight into alterations in the genetic cascade that accompanied
the evolution of vertebrate embryogenesis, we investigated the formation of the chordamesoderm in amphioxus embryos using
the genes Brachyury and fork head/HNF-3 as probes. Am(Bb)Bra1 and Am(Bb)Bra2 are homologues of the mouse Brachyury gene isolated from Branchiostoma belcheri. Molecular phylogenetic analysis suggests that the genes are independently duplicated in the amphioxus lineage. Both genes
are initially expressed in the involuting mesoderm of the gastrula, then in the differentiating somites of neurulae, followed
by the differentiating notochord and finally in the tail bud of ten-somite stage embryos. On the other hand, Am(Bb)fkh/HNF3-1, an amphioxus (B. belcheri) homologue of the fork head/HNF-3 gene, is initially expressed in the invaginating endoderm and mesoderm, then later in the differentiating notochord and in
the tail bud. With respect to these two types of genes, the formation of the notochord and tail bud in amphioxus embryos shows
similarity and dissimilarity with that of the notochord and tail bud in vertebrate embryos.
Received: 21 November 1996 / Accepted: 24 January 1997 相似文献
20.
Higashimoto K Soejima H Yatsuki H Joh K Uchiyama M Obata Y Ono R Wang Y Xin Z Zhu X Masuko S Ishino F Hatada I Jinno Y Iwasaka T Katsuki T Mukai T 《Genomics》2002,80(6):575-584
Human 11p15.5, as well as its orthologous mouse 7F4/F5, is known as the imprinting domain extending from IPL/Ipl to H19. OBPH1 and Obph1 are located beyond the presumed imprinting boundary on the IPL/Ipl side. We determined full-length cDNAs and complete genomic structures of both orthologues. We also investigated their precise imprinting and methylation status. The orthologues resembled each other in genomic structure and in the position of the 5' CpG island and were expressed ubiquitously. OBPH1 and Obph1 were predominantly expressed from the maternal allele only in placenta, with hypo- and not differentially methylated 5' CpG islands in both species. These results suggested that the imprinting domain would extend beyond the presumed imprinting boundary and that methylation of the 5' CpG island was not associated with the imprinting status in either species. It remains to be elucidated whether the gene is under the control of the KIP2/LIT1 subdomain or is regulated by a specific mechanism. Analysis of the precise genomic sequence around the region should help resolve this question. 相似文献