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Allogeneic gastric cancer cell-dendritic cell hybrids induce tumor antigen (carcinoembryonic antigen) specific CD8+ T cells 总被引:3,自引:0,他引:3
Matsumoto S Saito H Tsujitani S Ikeguchi M 《Cancer immunology, immunotherapy : CII》2006,55(2):131-139
The development of protocols for the ex vivo generation of dendritic cells (DCs) has led to intensive research of their potential
use in immunotherapy. Accumulating results show the efficacy of this treatment on melanomas which are highly immunogenic.
However, its efficacy remains unclear in other tumors. In this study, allogeneic gastric cancer cell–DC hybrids were used
to determine the efficacy of this type of immunotherapy in gastric cancer. Fusion cells of DC and allogeneic gastric cancer
cells were generated by polyethylene glycol (PEG) and electrofusion. These hybrids were used to induce tumor associated antigen
(TAA) specific cytotoxic T lymphocytes (CTLs). The DCs were successfully fused with the allogeneic gastric cancer cells resulting
in hybrid cells. These hybrid cells were functional as antigen-presenting cell because they induced allogeneic CD4+ T cells
proliferation. CD8+ T cells stimulated by the MKN-45-DC hybrid cells were able to kill MKN-45 when used for immunization.
The CTLs killed another gastric cancer cell line, MKN-1, as well as a melanoma cell line, 888mel, suggesting the recognition
of a shared tumor antigen. MKN-45 specific CTLs can recognize carcinoembryonic antigen (CEA), indicating that the killing
is due to tumor antigens as well as alloantigens. This approach suggests the possible use of allogeneic gastric cancer cell–DC
hybrids in DC based immunotherapy for gastric cancer treatment. 相似文献
2.
Hamasu T Inanami O Tsujitani M Yokoyama K Takahashi E Kashiwakura I Kuwabara M 《Apoptosis : an international journal on programmed cell death》2005,10(3):557-567
To elucidate radiobiological effects of hypoxia on X-ray-induced apoptosis, MOLT-4 cells were treated under four set of conditions: (1) both X irradiation and incubation under normoxia, (2) X irradiation under hypoxia and subsequent incubation under normoxia, (3) X irradiation under normoxia and subsequent incubation under hypoxia, and (4) both X irradiation and incubation under hypoxia, and the induction of apoptosis was examined by fluorescence microscopy. About 28–33% apoptosis was observed in cells treated under conditions 1 and 2, but this value was significantly reduced to around 18–20% in cells treated under conditions 3 and 4, suggesting that post-irradiation hypoxic incubation rather than hypoxic irradiation mainly caused the reduction of apoptosis. The activation and expression of apoptosis signal-related molecules SAPK/JNK, Fas and caspase-3 were also suppressed by hypoxic incubation. Effects of hypoxic incubation were canceled when cells were treated under conditions 3 and 4 with an oxygen-mimicking hypoxic cell radiosensitizer, whereas the addition of N-acetyl-L-cysteine again reduced the induction of apoptosis. From these results it was concluded that hypoxia reduced the induction of apoptosis by changing the intracellular redox state, followed by the regulation of apoptotic signals in X-irradiated MOLT-4 cells. 相似文献
3.
Masanori Kobayashi Shigetaka Shimodaira Kazuhiro Nagai Masahiro Ogasawara Hidenori Takahashi Hirofumi Abe Mitsugu Tanii Masato Okamoto Sun-ichi Tsujitani Seiichi Yusa Takefumi Ishidao Junji Kishimoto Yuta Shibamoto Masaki Nagaya Yoshikazu Yonemitsu 《Cancer immunology, immunotherapy : CII》2014,63(8):797-806
Objective
Dendritic cell (DC)-based cancer vaccines may have a significant benefit to patients with advanced pancreatic cancer. However, variations among clinical studies make it difficult to compare clinical outcomes. Here, we identified factors that determined the clinical benefits by analyzing data obtained at seven Japanese institutions that employed the same DC preparation and treatment regimens.Methods
Of 354 patients who met the inclusion criteria, 255 patients who received standard chemotherapy combined with peptide-pulsed DC vaccines were analyzed.Results
The mean survival time from diagnosis was 16.5 months (95 % CI 14.4–18.5) and that from the first vaccination was 9.9 months (95 % CI 8.0–12.9). Known prognostic baseline factors related to advanced pancreatic cancer, namely ECOG-PS, peritoneal metastasis, liver metastasis, and the prognostic nutrition index, were also representative. Importantly, we found that erythema reaction after vaccination was an independent and treatment-related prognostic factor for better survival and that OK-432 might be a good adjuvant enhancing the antitumor immunity during DC vaccination.Conclusions
This is the first report of a multicenter clinical study suggesting the feasibility and possible clinical benefit of an add-on DC vaccine in patients with advanced pancreatic cancer who are undergoing chemotherapy. These findings need to be addressed in well-controlled prospective randomized trials. 相似文献4.
Tatsuji Sakamoto Yuya Tsujitani Keiko Fukamachi Yuya Taniguchi Hideshi Ihara 《Applied microbiology and biotechnology》2010,86(4):1115-1124
Two distinct extracellular bifunctional proteins with β-L-arabinopyranosidase/α-D-galactopyranosidase activities were purified
from the culture filtrate of Fusarium oxysporum 12S. The molecular masses of the enzymes were estimated to be 55 (Fo/AP1) and 73 kDa (Fo/AP2) by SDS-PAGE. They hydrolyzed
both p-nitrophenyl β-L-arabinopyranoside and p-nitrophenyl α-D-galactopyranoside with different specificities. Fo/AP1 also showed low activity towards α-D-galactopyranosyl
oligosaccharides such as raffinose. Interestingly, both enzymes hydrolyzed larch wood arabinogalactan (releasing arabinose)
but not carob galactomannan, which has α-D-galactopyranosyl side chains. When larch wood arabinogalactan was incubated with
excess Fo/AP1 or Fo/AP2, both enzymes released approximately 10% of the total arabinose in the substrate. cDNAs encoding Fo/AP1
and Fo/AP2 (Foap1 and Foap2) were isolated by in vitro cloning. The coding sequences of Foap1 and Foap2 genes were 1,647 and 1,620 bp in length and encode polypeptides of 549 and 540 amino acids, respectively. The N-terminal
halves of both proteins had high similarity to putative conserved domains of the melibiase superfamily (Pfam account number
02065). The deduced amino acid sequences of the two enzymes indicate that they belong to glycosyl hydrolase family 27. Moreover,
the C-terminal regions of both proteins contain a putative family 35 carbohydrate-binding module. 相似文献
5.
Hidenori Takahashi Shigetaka Shimodaira Masahiro Ogasawara Shuichi Ota Masanori Kobayashi Hirofumi Abe Yuji Morita Kazuhiro Nagai Shunichi Tsujitani Masato Okamoto Yukio Suzuki Yoichi Nakanishi Yoshikazu Yonemitsu for the DC Vaccine Study Group at the Japanese Society of Immunotherapy Cell Therapy 《Cancer immunology, immunotherapy : CII》2016,65(9):1099-1111
6.
Thammapalo S Nagao Y Sakamoto W Saengtharatip S Tsujitani M Nakamura Y Coleman PG Davies C 《PLoS neglected tropical diseases》2008,2(7):e263
Background
Dengue is the most prevalent mosquito-borne virus, and potentially fatal dengue hemorrhagic fever (DHF) occurs mainly in secondary infections. It recently was hypothesized that, due to the presence of cross-immunity, the relationship between the incidence of DHF and transmission intensity may be negative at areas of intense transmission. We tested this hypothesis empirically, using vector abundance as a surrogate of transmission intensity.Methodology/Principal Findings
House Index (HI), which is defined as the percentage of households infested with vector larvae/pupae, was obtained from surveys conducted on one million houses in Thailand, between 2002 and 2004. First, the utility of HI as a surrogate of transmission intensity was confirmed because HI was correlated negatively with mean age of DHF in the population. Next, the relationship between DHF incidence and HI was investigated. DHF incidence increased only up to an HI of about 30, but declined thereafter. Reduction of HI from the currently maximal level to 30 would increase the incidence by more than 40%. Simulations, which implemented a recently proposed model for cross-immunity, generated results that resembled actual epidemiological data. It was predicted that cross-immunity generates a wide variation in incidence, thereby obscuring the relationship between incidence and transmission intensity. The relationship would become obvious only if data collected over a long duration (e.g., >10 years) was averaged.Conclusion
The negative relationship between DHF incidence and dengue transmission intensity implies that in regions of intense transmission, insufficient reduction of vector abundance may increase long-term DHF incidence. Further studies of a duration much longer than the present study, are warranted. 相似文献7.
This article describes graphical diagnostic methods for log odds ratio regression models. To study the effects of an additional covariate on log odds ratio regression analysis, three types of residual plots based on weighted least squares (WLS) are discussed: (i) added variable plot (partial regression plot), (ii) partial residual plot, and (iii) augmented partial residual plot. These plots provide diagnostic procedures for identifying heterogeneity of error variances, outliers, or nonlinearity of the model. They are especially useful for clarifying whether including a covariate as a linear term is appropriate, or whether quadratic or other nonlinear transformations are preferable. A well-known data set for case-control studies is analyzed to illustrate the residual plots. 相似文献
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