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Five weeks after the in vivo inoculation of potatoes ( Solanum tuberosum L.) with Agrobacterium. tumefaciens strain B6S3, bacteria were found in the non-differentiated cells of tumors (formed from xylem parenchyma or other living cells), in xylem cells at the site of inoculation, as well as in xylem cells of the adjacent stem.
Bacteria were attached by fibrillar aggregates to the tumor cell walls. They were also attached to a fibrillar mass which arose from agrobacteria connected to this mass in the tumor. Agrobacteria, singly or in pairs, were attached to an electron dense formation (possibly bacterial extracellular polysaccharides) found both inside the xylem cells of the stem adjacent to the tumor and at the site of inoculation. Some A. tumefaciens cells were attached by means of a pedestal-like structure at the inoculation site.
A possible function of the different means of attachment of A. tumefaciens in both nontransformed plant cells and tumors is discussed. 相似文献
Bacteria were attached by fibrillar aggregates to the tumor cell walls. They were also attached to a fibrillar mass which arose from agrobacteria connected to this mass in the tumor. Agrobacteria, singly or in pairs, were attached to an electron dense formation (possibly bacterial extracellular polysaccharides) found both inside the xylem cells of the stem adjacent to the tumor and at the site of inoculation. Some A. tumefaciens cells were attached by means of a pedestal-like structure at the inoculation site.
A possible function of the different means of attachment of A. tumefaciens in both nontransformed plant cells and tumors is discussed. 相似文献
3.
Waltraud Böhm Reinhold Schirmbeck J. Reimann 《Cancer immunology, immunotherapy : CII》1997,44(4):230-238
We demonstrate in a murine model that targeting an anti-viral T cell response to a growing tumor facilitates priming of a
tumor-associated antigen (TAA)-specific, rejecting T cell response. Murine P815 mastocytoma cells grow aggressively in a syngeneic
host. Transfected P815/S cells (expressing the hepatitis B surface antigen, HBsAg) also grow as subcutaneous tumors, but occasional
‘spontaneous’ rejections after transient growth are observed. Growth of P815/S tumors (but not of P815 tumors) is efficiently
suppressed by a CD8+ cytotoxic T lymphocyte (CTL)-dependent immune mechanism in mice primed to HBsAg by DNA–immunization. In hosts immunized against
HBsAg by DNA vaccination, HBsAg-specific CTL are generated. This specific CTL reactivity was targeted to s.c.-growing P815
tumors by intra tumor injections of either HBsAg-encoding plasmid DNA or viable P815/S cells; this treatment led to tumor
rejection in 70–80% of the tumor-bearing animals. All rejecting animals showed a CD8+ CTL-dependent resistance to subsequent challenges by native, non-transfected P815 tumors. Targeting an established anti-viral
(‘strong’) CTL response to a growing tumor hence is an efficient strategy to facilitate priming of a rejecting CTL response
against (‘weak’) TAA in this system.
Received: 18 December 1996 / Accepted: 6 February 1997 相似文献
4.
M. Margaret Prechel Yvonne Lozano Mark A. Wright J. Ihm M. R. I. Young 《Cancer immunology, immunotherapy : CII》1996,42(4):213-220
Lewis lung carcinoma (LLC-LN7) tumors stimulate myelopoiesis and increase the presence of granulocyte/macrophage (GM) progenitor
cells having natural suppressor activity. Treatment of these tumor-bearing mice with interleukin-12 (IL-12) resulted in minimal
immune modulation. The objective of this study was to determine whether eliminating natural suppressor activity would allow
for immune stimulation by IL-12. Treatment of LLC-LN7 tumor-bearing mice with vitamin D3 eliminated natural suppressor activity. In mice that were first treated with vitamin D3 and then also with IL-12, there was stimulation of splenic T cell proliferation in response to immobilized anti-CD3 plus
IL-2. In addition, spleen and lymph node cells from vitamin-D3/IL-12-treated tumor-bearing mice became stimulated in response to autologous tumor to produce interferon γ (IFNγ), although
IL-2 production was not stimulated. A prominent effect of the combined vitamin-D3/IL-12 treatment regimen was the synergistic augmentation of autologous tumor-specific cytolytic activity within the regional
lymph nodes. The generation of these tumor-specific effector cells required the presence of the tumor mass since such activity
was not elicited in the lymph nodes of mice from which the tumors had been surgically excised. The results of this study show
that, after treatment of tumor bearers with vitamin D3 to eliminate GM-suppressor cells, IL-12 can induce select regional antitumor immune responses, particularly IFNγ production
and cytolysis by regional lymph node cells of autologous tumor.
Received: 15 December 1995 / Accepted: 22 March 1996 相似文献
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Ussama M. Abdel-Motal Kim Wigglesworth Uri Galili 《Cancer immunology, immunotherapy : CII》2009,58(10):1545-1556
α-Gal glycolipids capable of converting tumors into endogenous vaccines, have α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R) and
are extracted from rabbit RBC membranes. α-Gal epitopes bind anti-Gal, the most abundant natural antibody in humans constituting
1% of immunoglobulins. α-Gal glycolipids insert into tumor cell membranes, bind anti-Gal and activate complement. The complement
cleavage peptides C5a and C3a recruit inflammatory cells and APC into the treated lesion. Anti-Gal further opsonizes the tumor
cells and targets them for effective uptake by recruited APC, via Fcγ receptors. These APC transport internalized tumor cells
to draining lymph nodes, and present immunogenic tumor antigen peptides for activation of tumor specific T cells. The present
study demonstrates the ability of α-gal glycolipids treatment to prevent development of metastases at distant sites and to
protect against tumor challenge in the treated mice. Adoptive transfer studies indicate that this protective immune response
is mediated by CD8+ T cells, activated by tumor lesions turned vaccine. This T cell activation is potent enough to overcome
the suppressive activity of Treg cells present in tumor bearing mice, however it does not elicit an autoimmune response against
antigens on normal cells. Insertion of α-gal glycolipids and subsequent binding of anti-Gal are further demonstrated with
human melanoma cells, suggesting that intratumoral injection of α-gal glycolipids is likely to elicit a protective immune
response against micrometastases also in cancer patients. 相似文献
7.
Hara H Kobayashi A Narumi K Kondoh A Yoshida K Nishimoto T Ohashi M Higashihara E Ohnami S Yoshida T Aoki K 《Cancer immunology, immunotherapy : CII》2009,58(7):1007-1021
One of the major challenges in the treatment of solid cancers by allogenic hematopoietic stem cell transfer (alloHSCT) is
the specific enhancement of antitumor immunity. Interferon (IFN) is a cytokine with pleiotropic biological functions including
an immunomoduration, and our preclinical studies have shown that an intratumoral IFN-α gene transfer induced strong local
tumor control and systemic tumor-specific immunity. In the present study, we examined whether the IFN-α gene transfer could
enhance recognition of tumor-associated antigens by donor T cells and augment the antitumor activity of alloHSCT. First, when
a mouse IFN-α adenovirus vector (Ad-mIFN) was injected into subcutaneous xenografts of syngeneic renal and colon cancer cells,
tumor growth was significantly suppressed in a dose-dependent manner. A significant tumor cell death and infiltration of immune
cells was recognized in the Ad-mIFN-injected tumors, and the dendrtic cells isolated from the tumors showed a strong Th1-oriented
response. The antitumor effect of Ad-mIFN was then examined in a murine model of minor histocompatibility antigen-mismatched
alloHSCT. The intratumoral IFN-α gene transfer caused significant tumor suppression in the alloHSCT recipients, and this suppression
was evident not only in the gene-transduced tumors but also in simultaneously inoculated distant tumors which did not receive
the vector injection. A cytotoxicity assay showed specific tumor cell lysis by donor T cells responding to IFN-α. Graft-versus-host
disease was not exacerbated serologically or clinically in the mice treated with IFN-α. This combination strategy deserves
evaluation in future clinical trials for human solid cancers. 相似文献
8.
Timothy E. Kute Lori Savage John R. StehleJr Jung W. Kim-Shapiro Michael J. Blanks James Wood James P. Vaughn 《Cancer immunology, immunotherapy : CII》2009,58(11):1887-1896
An understanding of model systems of trastuzumab (Herceptin) resistance is of great importance since the humanized monoclonal
antibody is now used as first line therapy with paclitaxel in patients with metastatic Her2 overexpressing breast cancer,
and the majority of their tumors has innate resistance or develops acquired resistance to the treatment. Previously, we selected
trastuzumab-resistant clonal cell lines in vitro from trastuzumab-sensitive parental BT-474 cells and showed that cloned trastuzumab-resistant
cell lines maintain similar levels of the extracellular Her2 receptor, bind trastuzumab as efficiently as the parental cells,
but continue to grow in the presence of trastuzumab and display cell cycle profiles and growth rates comparable to parental
cells grown in the absence of trastuzumab (Kute et al. in Cytometry A 57:86–93, 2004). We now show that trastuzumab-resistant and trastuzumab-sensitive cells both surprisingly display trastuzumab-mediated growth
inhibition in athymic nude mice. This demonstrates that resistance developed in vitro is not predictive of resistance in vivo.
The observation that in vitro resistant cells are sensitive to trastuzumab in vivo could be explained by antibody dependant
cellular cytotoxicity (ADCC). Therefore, both parental and trastuzumab-resistant cells were assayed for ADCC in real time
on electroplates with and without trastuzumab in the presence of a natural killer cell line (NK-92), and granulocyte or mononuclear
cellular fractions isolated from human peripheral blood. Mononuclear cells and NK-92 cells were more effective in killing
both parental and trastuzumab-resistant cells in the presence of trastuzumab. Both trastuzumab-resistant cells and trastuzumab-sensitive
cells showed similar susceptibility to ADCC despite displaying divergent growth responses to trastuzumab. The granulocyte
fraction was able to kill these cells with equal efficacy in the presence or absence of trastuzumab. These results support
a model of trastuzumab tumor cell killing in vivo mediated primarily by ADCC from the mononuclear fraction of innate immune
cells and suggest that in the clinical setting not only should changes in signaling transduction pathways be studied in acquired
tumor resistance to trastuzumab, but also mechanisms by which tumors impede immune function should be evaluated. 相似文献
9.
Bergman I Basse PH Barmada MA Griffin JA Cheung NK 《Cancer immunology, immunotherapy : CII》2000,49(4-5):259-266
Antibodies can direct tumor cell lysis by activating complement-mediated and cell-mediated cytoxicities (antibody-dependent
cell-mediated cytotoxicity, ADCC). Clinical translation of these effects into successful cancer therapy has been slow. Choosing
an appropriate animal model to test new therapeutic strategies is difficult because of species differences in immunological
effector functions. In previous work, we found that an unmodified anti-ganglioside mouse IgG3 monoclonal antibody (mAb), 3F8,
could successfully treat clinical tumors in humans and experimental tumors in rats but not experimental tumors in mice. We
explored the reasons for this species difference by performing in vitro antibody-dependent cytotoxicity assays comparing the
potency of polymorphonuclear neutrophils (PMN), natural killer (NK) cells and complement from the three species: mouse, rat
and human. 3F8-dependent complement-mediated cytotoxicity produced more than 70% specific release when human and rat sera
were used and only 20% with mouse serum. PMN-mediated ADCC was 35%–70% with human effectors, 25%–60% with rat and undetectable
with mouse. Human eosinophils did not contribute to this ADCC. Cytotoxicity utilizing interleukin-2-activated NK cells was
antibody-independent in all three species but the specific release was 60%–70% with human and rat NK cells and 10% with mouse
NK cells. These data suggest that, for mouse IgG3, the rat may provide a more relevant rodent model than the mouse for testing
the in vivo antitumor effects of monoclonal antibodies.
Received: 20 January 2000 / Accepted: 24 March 2000 相似文献
10.
In this paper we present a two-compartment model for tumor dormancy based on an idea of Zetter [1998, Ann. Rev. Med. 49, 407–422] to wit: The vascularization of a secondary (daughter) tumor can be suppressed by an inhibitor originating from a larger primary (mother) tumor. We apply this idea at the avascular level to develop a model for the remote suppression of secondary avascular tumors via the secretion of primary avascular tumor inhibitors. The model gives good agreement with the observations of [De Giorgi et al., 2003, Derm. Surgery 29, 664–667]. These authors reported on the emergence of a polypoid melanoma at a site remote from a primary polypoid melanoma after excision of the latter. The authors observed no recurrence of the melanoma at the primary site, but did observe secondary tumors at secondary sites 5–7 cm from the primary site within a period of 1 month after the excision of the primary site. We attempt to provide a reasonable biochemical/cell biological model for this phenomenon. We show that when the tumors are sufficiently remote, the primary tumor will not influence the secondary tumor while, if they are too close together, the primary tumor can effectively prevent the growth of the secondary tumor, even after it is removed. It should be possible to use the model as the basis for a testable hypothesis. 相似文献
11.
Tumor-specific T-bodies: towards clinical application 总被引:6,自引:1,他引:5
Zelig Eshhar 《Cancer immunology, immunotherapy : CII》1997,45(3-4):131-136
Unlike antibodies, T cells are well suited to penetrate and destroy solid tumors. The T-body approach combines antibody recognition
and T cells effector function. It is based on T cells expressing chimeric receptors composed of antibody-derived Fv or scFv
as their extracellular recognition elements joined to lymphocyte triggering molecules. This receptors can redirect the specificity
of T cells in an MHC independent manner. Upon encountering their target cells, T-bodies are able to undergo specific stimulation
for interleukin/cytokine production, and kill hapten-modified or tumor cells in model systems both in vitro and in vivo. T cells expressing chimeric receptors made of antitumor antibodies are able to discriminate between a tumor and normal cell
with negligible bystander cytotoxicity. Further studies should be carried out to evaluate and optimize the persistence, homing
patterns and reactivation potential of T-bodies in the body.
Accepted: 14 October 1997 相似文献
12.
Julie A. McEarchern David G. Besselsen Emmanuel T. Akporiaye 《Cancer immunology, immunotherapy : CII》1999,48(2-3):63-70
Transforming growth factor β (TGFβ) is an immunosuppressive cytokine that contributes to the immunological escape of tumor
cells. In a previous study we demonstrated that inhibition of TGFβ production by EMT6 murine mammary tumor cells expressing
an antisense TGF-β transgene reduces their tumorigenicity. On the basis of this observation we hypothesized that down-regulation
of TGFβ production coupled with interferon γ (IFNγ) stimulation would induce an immune response superior to that generated
by either strategy alone. In this study, EMT6 tumor cells expressing antisense TGFβ were transduced with the murine IFNγ gene.
Tumor cells expressing either or both transgenes grew more slowly than mock-transduced tumors. Dual-transgene-expressing tumor
cells were more immunogenic than tumor cells expressing either transgene alone. Studies in mice depleted of T cell subsets
indicated that CD8+ T cells are the primary effectors of the antitumor activity observed. These results suggest that down-regulation of immunosuppression
combined with cytokine-mediated immune augmentation is a useful strategy to improve antitumor immunity.
Received: 6 October 1998 / Accepted: 15 January 1999 相似文献
13.
Brain cancer cells invade early on surrounding parenchyma, which makes it impossible to surgically remove all tumor cells and thus significantly worsens the prognosis of the patient. Specific structural elements such as multicellular clusters have been seen in experimental settings to emerge within the invasive cell system and are believed to express the systems' guidance toward nutritive sites in a heterogeneous environment. Based on these observations, we developed a novel agent-based model of spatio-temporal search and agglomeration to investigate the dynamics of cell motility and aggregation with the assumption that tumors behave as complex dynamic self-organizing biosystems. In this model, virtual cells migrate because they are attracted by higher nutrient concentrations and to avoid overpopulated areas with high levels of toxic metabolites. A specific feature of our model is the capability of cells to search both globally and locally. This concept is applied to simulate cell-surface receptor-mediated information processing of tumor cells such that a cell searching for a more growth-permissive place "learns" the information content of a brain tissue region within a two-dimensional lattice in two stages, processing first the global and then the local input. In both stages, differences in microenvironment characteristics define distinctions in energy expenditure for a moving cell and thus influence cell migration, proliferation, agglomeration, and cell death. Numerical results of our model show a phase transition leading to the emergence of two distinct spatio-temporal patterns depending on the dominant search mechanism. If global search is dominant, the result is a small number of large clusters exhibiting rapid spatial expansion but shorter lifetime of the tumor system. By contrast, if local search is dominant, the trade-off is many small clusters with longer lifetime but much slower velocity of expansion. Furthermore, in the case of such dominant local search, the model reveals an expansive advantage for tumor cell populations with a lower nutrient-depletion rate. Important implications of these results for cancer research are discussed. 相似文献
14.
Stem cells and brain cancer 总被引:15,自引:0,他引:15
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目的:培养鼠肝癌H22细胞,直接注射法制作ICR小鼠肝癌原位移植瘤,为后续实验奠定基础。方法:鼠肝癌H22细胞体外培养,将调整好的对数生长期的肝癌细胞直接注射小鼠肝脏,2周后解剖观察,并进行组织HE染色。结果:所有实验小鼠均可见肿瘤生长,HE染色示肝细胞肝癌。结论:直接注射法制作ICR小鼠肝癌原位移植瘤模型简便易行,值得推广应用。 相似文献
17.
Apoptosis is also known as programmed cell death. Apoptosis plays an essential role in maintaining normal tissue and cell physiology in multicellular organisms. Clearance of aberrant or pre-cancerous cells occurs through the induction of apoptosis. It has been reported that many tumors and tumor cell lines have dysfunctional apoptosis signaling, causing these tumors to escape immune monitoring and internal cellular control mechanisms. One potential cause of this dysfunctional apoptosis is the tumor suppressor p53, an important regulator of growth arrest and apoptosis that is mutated in over 50% of all cancers. Retinoids have great potential in the areas of cancer therapy and chemoprevention. While some tumor cells are sensitive to the growth inhibitory effects of natural retinoids such as all-trans-retinoic acid (ATRA), many ovarian tumor cells are not. 6-[3-(1-Admantyl)]-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) and fenretinide N-[4-hydroxyphenyl] retinamide (4-HPR) are conformationally restricted synthetic retinoids that induce growth arrest and apoptosis in both ATRA-sensitive and ATRA-resistant ovarian tumor cell lines. Recently, we have identified the molecular pathways of apoptosis induced by treatment of ovarian carcinoma cells with mutated p53 by CD437 and 4-HPR. 相似文献
18.
Yuvaraja B Thyavihally Hemant B Tongaonkar Sangeeta B Desai 《International Seminars in Surgical Oncology : ISSO》2005,2(1):18
Background
Mixed epithelial and stromal tumor (MEST) is a distinctive benign composite neoplasm of the kidney predominantly seen in females mostly in the perimenopausal period. Although these tumors are known to arise from renal pelvis, our case was distinct in that it had no intrapelvic component growing in exophytic fashion.Case report
A 35 year old female patient presented to us with vague abdominal pain. She had undergone excision of bilateral ovarian cystic masses for cystic teratoma twelve years earlier. A computed tomography scan of abdomen and pelvis showed a 9 × 7 cm uniformly solid mass with poor contrast enhancement situated in the inferomedial aspect of the left kidney. On exploration, the mass was arising from the inferior and anterior aspect of left renal pelvis, and was attached to it with a narrow pedicle. There was no adherence or attachment to the renal parenchyma. The mass was excised preserving the kidney. Microscopically, the tumor was composed of large collagenized areas containing bundles of spindle cells and several 'microcysts' lined by cuboidal epithelium suggestive of a benign mixed epithelial stromal tumor.Discussion
Mixed epithelial tumors usually present in perimenopausal women as a partially cystic mass. Tumors are composed of irregular mixtures of cystic and solid areas, glands with variable complexity and distribution and the stromal component is characterized by a spindle cell proliferation. Commonly, it arises from the renal parenchyma and pelvis and nephrectomy is advocated to manage these tumors.Conclusion
MEST is a distinctive benign tumor of the kidney that should be distinguished from other renal neoplasms. MEST arising from the renal pelvis and growing exophytically is a rare entity. The overall prognosis is favorable.19.
Yang Q Goding S Hagenaars M Carlos T Albertsson P Kuppen P Nannmark U Hokland ME Basse PH 《Cancer immunology, immunotherapy : CII》2006,55(6):699-707
We have recently shown that adoptively transferred, IL-2-activated natural killer (A-NK) cells are able to eliminate well-established
B16-F10.P1 melanoma lung metastases. However, some B16-F10.P1 lung metastases were resistant to infiltration by the A-NK cells
and also resistant to the A-NK cell treatment. The infiltration-resistant (I-R) B16-F10.P1 metastases had a unique “compact”
morphology compared to the “loose” morphology of the infiltration-permissive (I-P) metastases. Here, we show that I-P loose
tumors and I-R compact tumors are also found in lung metastases of mouse Lewis lung carcinoma (3LL), MCA-102 sarcoma, and
MC38 colon carcinoma as well as rat MADB106 mammary carcinoma origin. Furthermore, the infiltration resistance of the compact
tumors is not restricted to A-NK cells, since PHA and IL-2 stimulated CD8+ T-cells (T-LAK cells) also infiltrated the compact
tumors poorly. Analyses of tumors for extracellular matrix (ECM) components and PECAM-1+ vasculature, revealed that the I-R lesions are hypovascularized and contain very little laminin, collagen and fibronectin.
In contrast, the I-P loose tumors are well-vascularized and they contain high amounts of ECM components. Interestingly, the
distribution pattern of ECM components in the I-P loose tumors is almost identical to that of the normal lung tissue, indicating
that these tumors develop around the alveolar walls which provide the loose tumors with both a supporting tissue and a rich
blood supply. In conclusion, tumor infiltration by activated NK and T cells correlates with the presence of ECM components
and PECAM-1+ vasculature in the malignant tissue. Thus, analysis of the distribution of ECM and vasculature in tumor biopsies may help
select patients most likely to benefit from cellular adoptive immunotherapy. 相似文献
20.
Tumors grow more readily in the brain than in the periphery, in part due to immune privilege. Differences in both afferent and efferent components of the immune response contribute to this lower level of responsiveness. On the afferent side, despite the lack of lymphatic vessels in the brain, antigens from brain arrive in lymph nodes and spleen by several routes, and the route taken may influence the type of response generated. Work with viruses and soluble antigens in mice has shown that the intracerebral location and the volume of the inoculation influence the strength of the cytotoxic T cell response. We examined whether these factors influence the T cell response against experimental brain tumors in mice. Placement of tumor cells in the cerebral ventricles instead of the parenchyma generated an immune response sufficient to increase survival time. A large volume of an intraparenchymal infusion of tumor cells caused spread of cells to the ventricles, and resulted in longer survival time relative to a small volume infusion. Infusion of the same dose of radiolabeled tumor cells in either a small volume or a large volume allowed tracking of potential tumor antigens to the periphery. Both modes of infusion resulted in similar levels of radioactivity in blood, spleen and kidney. Unexpectedly, cells infused intraparenchymally in a small volume, compared to a large volume, resulted in (1) more radioactivity in cervical lymph nodes (parotid and deep cervical lymph nodes), (2) a greater number of CD11b+/Gr1+ myeloid suppressor cells in the tumors, and (3) fewer CD8+ cells within the tumor mass. Consistent with these observations, providing a stronger afferent stimulus by giving a concurrent subcutaneous injection of the same tumor cells infused into the brain increased CD8+ T cell infiltration of the tumor in the brain. These results suggest that the immune response elicited by antigens that drain predominantly to the cervical lymph nodes may be less effective than responses elicited at other lymph nodes, perhaps due to immunosuppressive cells. Directing therapies to the optimal peripheral sites may improve immune responses against brain tumors. 相似文献