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Hiroyuki Katoh

Publications and source records attributed to Hiroyuki Katoh.

At least 37 records · Page 2Linked to original sources
PubMed2005

Prediction of lymphatic invasion/lymph node metastasis, recurrence, and survival in patients with gastric cancer by cDNA array-based expression profiling.

BACKGROUND: We assessed the predictability of various classes of gastric carcinoma defined by clinicopathological parameters, such as invasiveness and clinical outcomes, using cDNA array data obtained from 54 cases. MATERIALS AND METHODS: We searched an optimal combination of genes to discriminate the classes defined with the clinicopathological parameters by using a feature subset selection algorithm, which was applied to a set of genes preselected on the basis of statistical difference in expression (two-sided t test, P < or = 0.05). With the selected features (gene set), we evaluated the predictability of each parameter in a leave-one-out cross-validation test. RESULTS: We successfully selected sets of genes for which the classifier predicted better versus worse overall survival (tumor-specific death) and tumor-free survival (recurrence), with respective classification rates of 94 and 92%. A contingency table analysis (chi2 test) and Cox proportional hazard model analysis revealed that lymph node metastasis is the most important factor (confounding factor) in patients' prognoses and risks of recurrence. The feature subset selection procedure successfully extracted expression patterns characteristic of lymph node metastasis and lymphatic vessel invasion, yielding 92 and 98% prediction accuracies for these respective factors. CONCLUSION: We conclude that expression profiling using feature subset selection provides a powerful means of stratification of gastric cancer patients in regard to the prognostic factors. Further studies should be warranted to apply this method to personalization of the treatment options.

Adenocarcinoma, Mucinous↗
PubMed2005

Right- and left-sided colorectal cancers display distinct expression profiles and the anatomical stratification allows a high accuracy prediction of lymph node metastasis.

Accurate preoperative prediction of lymph node metastasis and degree of tumor invasion would facilitate an appropriate decision of the extent of surgical resection of cancers to reduce unnecessary complication or to minimize the risk of recurrence in patients. We analyzed gene expression profiles characteristic of the invasiveness of colorectal carcinoma in a total of 89 cases, using a cDNA array and pattern classification algorithms. We set binary classes for a panel of clinicopathologic parameters, each of which was divided at different levels for categories (discrete) or values (continuous). We searched an optimal combination of genes to discriminate the classes by using of a feature subset selection algorithm, which was applied to a set of genes preselected on the basis of statistical difference in expression (two-sided t test, P < or = 0.05). We used a sequential forward feature selection which additively searched a combination of genes, giving a minimal leave-one-out classification error rate of a k-nearest neighbor classifier. In the process of gene preselection, we found a remarkable difference in the expression pattern of genes according to the anatomical location of cancers. The difference was most prominent when the classes were set for cecum, ascending colon, transverse colon, and descending colon (CATD) versus sigmoid colon and rectum (SR). By stratifying these two locations, we were able to extract gene expression profiles characteristic of the classes of the presence versus absence of lymph node metastasis, lymphatic invasion, vascular invasion and degree of mural invasion, and pathological stages, with an accuracy of more than 90%. These results suggest that colorectal cancers harbor distinct molecular pathophysiological statuses according to their right-to-left locations, of which stratification is important for pattern classification of cDNA array data.

Adult↗
PubMed2005

The incidence of reflux oesophagitis after eradication therapy for Helicobacter pylori.

BACKGROUND: Although several studies have indicated that Helicobacter pylori eradication develops reflux oesophagitis, others reported that its eradication had a beneficial effect on reflux symptoms. The results are still controversial. OBJECTIVE: To study whether H. pylori eradication increases the occurrence rate of reflux oesophagitis in patients with peptic ulcers. METHOD: One hundred and two consecutive patients who had peptic ulcers and were H. pylori-positive by C-urea breath testing were followed prospectively. They all received 1-week triple therapy and underwent endoscopy at 1-year intervals or when relapse of the peptic ulcer or occurrence of reflux oesophagitis was suspected. RESULTS: Reflux oesophagitis developed in 32 (31.4%) out of 102 patients and they were of grade A (27 patients) and grade B (five patients) by the Los Angeles classification System. H. pylori infection was cured in 77 (75.5%) out of 102 patients. There was no significant difference in age (53.4+/-1.2 vs. 53.9+/-1.4 years, P = 0.43), gender (male/female, 29/3 vs. 53/17, P = 0.14), ulcer location (gastric/duodenal/both, 15/12/5 vs. 35/26/9, P = 0.97), H. pylori status (persistent/cured, 9/23 vs. 16/54, P = 0.57) or length of follow-up time (355+/-32 vs. 348+/-23 days, P = 0.30) between the 32 patients with reflux oesophagitis and the other 70 patients. Only the presence of hiatal hernia before therapy was significant for the prevalence of reflux oesophagitis by the log-rank test (P = 0.002), and the Cox proportional hazard models confirmed these findings (odds ratio, 3.46; 95% confidence interval, 1.64-7.30; P = 0.0012). CONCLUSIONS: The eradication of H. pylori did not increase the prevalence of reflux oesophagitis, and only the presence of hiatal hernia before therapy was significantly related to the development of reflux oesophagitis.

Anti-Bacterial Agents↗
PubMed2005

Chondroitinase ABC combined with neural stem/progenitor cell transplantation enhances graft cell migration and outgrowth of growth-associated protein-43-positive fibers after rat spinal cord injury.

We previously reported that the transplantation of neural stem/progenitor cells (NSPCs) can contribute to the repair of injured spinal cord in adult rats and monkeys. In some cases, however, most of the transplanted cells adhered to the cavity wall and failed to migrate and integrate into the host spinal cord. In this study we focused on chondroitin sulfate proteoglycan (CSPG), a known constituent of glial scars that is strongly expressed after spinal cord injury (SCI), as a putative inhibitor of NSPC migration in vivo. We hypothesized that the digestion of CSPG by chondroitinase ABC (C-ABC) might promote the migration of transplanted cells and neurite outgrowth after SCI. An in vitro study revealed that the migration of NSPC-derived cells was inhibited by CSPG and that this inhibitory effect was attenuated by C-ABC pre-treatment. Consistently, an in vivo study of C-ABC treatment combined with NSPC transplantation into injured spinal cord revealed that C-ABC pre-treatment promoted the migration of the transplanted cells, whereas CSPG-immunopositive scar tissue around the lesion cavity prevented their migration into the host spinal cord in the absence of C-ABC pre-treatment. Furthermore, this combined treatment significantly induced the outgrowth of a greater number of growth-associated protein-43-positive fibers at the lesion epicentre, compared with NSPC transplantation alone. These findings suggested that the application of C-ABC enhanced the benefits of NSPC transplantation for SCI by reducing the inhibitory effects of the glial scar, indicating that this combined treatment may be a promising strategy for the regeneration of injured spinal cord.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed2005

Superficially spreading cholangiocarcinoma.

Cholangiocarcinoma of a raised, elevated type, not an infiltrative type, may be accompanied with superficial spread in the contiguous mucosa. We report a case of an extrahepatic cholangiocarcinoma that showed a specific cholangiographic finding of extensive superficial spread. The patient was a 62-yr-old man. Cholangiography revealed an elevated lesion in the middle of the bile duct, which was surrounded by irregularity of the bile duct wall extensively. We accurately diagnosed the tumor extent by percutaneous transhepatic cholangioscopy and achieved radical resection without hepatic resection. The margins were tumor-negative by microscopy. In conclusions, it is important to accurately diagnose the extent of superficial spread preoperatively by cholangioscopy and biopsy, and decide the resecting lines to make margins tumor-negative.

Bile Duct Neoplasms↗
PubMed2005

Aberrant expression of HOX genes in human invasive breast carcinoma.

HOX genes are known not only as master genes that control the morphogenesis, but also as regulator genes that maintain tissue or organ specificity in the adult body. We hypothesized that dysregulated expression of HOX genes was associated with tumor development and malignant progression such as invasion and metastasis. In this study, we analyzed the expression patterns of 39 HOX genes in human invasive ductal breast cancer tissues and normal tissues by the real-time RT-PCR method. We found 11 HOX genes (HOXA1, A2, A3, A5, A9, C11, D3, D4, D8, D9 and D10) expression levels of which were significantly different between cancerous and normal tissues. All 10 genes except HOXC11 were expressed at lower levels in cancerous tissues than normal tissues. Comparing expression levels of each HOX gene among the different types of cancer tissues, the expression level of HOXB7 was lower in lymph node metastasis-positive cancer tissues than negative cancer tissues; those of HOXD12 and D13 were higher in progesterone receptor-positive cancer tissues than negative cancer tissues; and the expression level of HOXC5 was lower in cancerous tissues with mutated-type p53 than in normal and cancerous tissues with wild-type p53. These results suggest that the aberrant expression of HOX genes is related to the development of breast cancer and malignant behavior of cancer cells.

Adult↗
PubMed2004

Liposome-encapsulated CpG oligodeoxynucleotides as a potent adjuvant for inducing type 1 innate immunity.

Unmethylated cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG-ODNs) exhibit potent immunostimulating activity by binding with Toll-like receptor 9 (TLR9) expressed on antigen-presenting cells. Here, we show that CpG-ODN encapsulated in cationic liposomes (CpG-liposomes) improves its incorporation into CD11c(+) dendritic cells (DCs) and induces enhanced serum interleukin (IL)-12 levels compared with unmodified CpG-ODN. CpG-liposome potently activated natural killer (NK) cells (84.3%) and NKT cells (48.3%) to produce interferon-gamma (IFN-gamma), whereas the same dose of unmodified CpG-ODN induced only low numbers of IFN-gamma-producing NK cells (12.7%) and NKT cells (1.6%) to produce IFN-gamma. In contrast with the NKT cell agonist alpha-galactosylceramide, which induces both IFN-gamma and IL-4 production by NKT cells, CpG-liposome only induced IFN-gamma production by NKT cells. Such potent adjuvant activities of CpG-liposome were absent in TLR9-deficient mice, indicating that CpG-liposome was as effective as CpG-ODN in stimulating type 1 innate immunity through TLR9. In addition to TLR9, at least two other factors, IL-12 production by DCs and direct contact between DCs and NK or NKT cells, were essential for inducing type 1 innate immunity by CpG-liposome. Furthermore, ligation of TLR9 by CpG-liposome coencapsulated with ovalbumin (OVA) caused the induction of OVA-specific CTLs, which exhibited potent cytotoxicity against OVA-expressing tumor cells. These results indicate that CpG-liposome alone or combined with tumor antigen protein provides a promising approach for the prevention or therapy of tumors.

Adjuvants, Immunologic↗
PubMed2004

Mating-induced mating-type cassette conversion in Saccharomyces cerevisiae.

We have previously reported that the HMRa-bearing restriction fragment of a rho degrees sir4-11 strain (HMLalpha-MATalpha-HMRa), which acts as an alpha-mater because of being rho degrees , changes its electrophoretic mobility when the strain mates with a certain group of a-mating strains (HMLalpha-MATa-HMRa). In this study, we found that the sir4-11 strain being rho degrees was not essential for this phenomenon and also that the altered form of the fragment contained HMRalpha in place of HMRa. Furthermore, we observed conversion of HMLa to HMLalpha in the cross in which a sir4-11 HMLa-MATalpha-HMRalpha strain was mated with a representative of the above-mentioned a-mating strain. In addition, when this a-mating strain was mated with a SIR(+) HMLalpha-MATa-HMRalpha strain, the resultant diploid was found to be HMLalpha/HMLalpha MATa/MATalphaHMRa/HMRalpha, indicating that conversion of MATa to MATalpha had taken place in the course of mating. From all these observations, we conclude that there is a group of S. cerevisiae strains that carries factor(s) that induces conversion of a mating-type cassette of the mating partner to alpha mating-type cassette and that this mating type cassette conversion takes place in all three mating type loci, HML, MAT and HMR, if the loci are in the non-silenced condition.

Base Sequence↗
PubMed2004

Difference of caveolin-1 expression pattern in human lung neoplastic tissue. Atypical adenomatous hyperplasia, adenocarcinoma and squamous cell carcinoma.

Caveolin-1 has been implicated in cellular transformation and tumorigenesis. We assessed lung cancer specimens for caveolin-1 expression immunohistochemistry. A majority of the cell types in the lung and the bronchial epithelium normally exhibited positive staining for caveolin-1. In adenocarcinomas (ADs) of positive staining for caveolin-1, pT1 tumors exhibited significantly higher staining than pT2-pT4 tumors (P=0.0240). In squamous cell carcinomas (SCCs), pT1-pT2 tumors expressed significantly lower expression levels than pT3-pT4 tumors (P=0.0175). In AD, loss of caveolin-1 may be essential for tumor extension and dedifferentiation. In contrast, caveolin-1 overexpression may be correlated with tumor extension in SCC.

Adenocarcinoma↗
PubMed2004

Outcome of duodenum-preserving resection of the head of the pancreas for intraductal papillary-mucinous neoplasm.

BACKGROUND: The standard surgical procedure for intraductal papillary-mucinous neoplasm of the pancreatic head is pylorus-preserving pancreatoduodenectomy. A less extensive resection may be justified because most intraductal papillary-mucinous neoplasms are benign or of low-grade malignancy. AIMS AND METHODS: The outcome of duodenum-preserving pancreatic head resection with preservation of the main bile duct was evaluated retrospectively in 13 patients with a branch-type intraductal papillary-mucinous neoplasm in the head of the pancreas and with a median (range) follow-up of 60.0 (0.3-99.5) months. RESULTS: Post-operative complications included anastomotic leakage (n=3), bile duct perforation (n=1), intra-abdominal bleeding (n=3), delayed gastric emptying (n=2) and death (n=2). All the resection margins were clear of tumour on histological examination. Ten of 11 patients maintained over 90% of their pre-operative body weight. Glucose tolerance improved in 4 of 11 evaluable patients, was unchanged in 6 and worsened in 1 patient. Biliary scintigraphy showed that bile flow was delayed compared with that before surgery (8.8 +/- 1.1 vs. 19.6 +/- 4.6 min; p = 0.03). Neither recurrence nor metastasis was observed. CONCLUSION: The results of duodenum-preserving pancreatic head resection for branch duct-type intraductal papillary-mucinous neoplasm were satisfactory and provided a good quality of life.

Adenocarcinoma, Mucinous↗
PubMed2004

Chemokines in bronchiolar epithelium in the development of chronic obstructive pulmonary disease.

The inflammatory chemokines interleukin-8, macrophage inflammatory protein-1alpha, and monocyte chemoattractant protein-1, are reportedly involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Although bronchiolar epithelial cells and macrophages are known to be the cellular sources, the relative contribution of each cell type remains to be elucidated. In the present study, we first quantified cytokine mRNA in human bronchiolar epithelial cells and macrophages obtained using laser-capture microdissection and explored the relationship with early-stage COPD. Only in bronchiolar epithelial cells were interleukin-8, macrophage inflammatory protein-1alpha, and monocyte chemoattractant protein-1 mRNA levels higher in smokers with airflow limitation and/or emphysema than those in never-smokers or smokers without either airflow limitation or emphysema. No difference was observed in macrophages. Complementary DNA (cDNA) array further revealed the overexpression of CC chemokine receptor 2 in bronchiolar epithelial cells from smokers with airflow limitation and/or emphysema. This study supports the role of bronchiolar epithelium as the source of increased inflammatory chemokine levels in the early development of COPD and also demonstrates the potential use of laser-capture microdissection, combined with reverse transcriptase-polymerase chain reaction and cDNA microarrays, to investigate functional profiles of individual structural and inflammatory cells in human lungs.

Adult↗
PubMed2004

Gene-expression profile changes correlated with tumor progression and lymph node metastasis in esophageal cancer.

PURPOSE: The purpose of this research was to identify molecular clues to tumor progression and lymph node metastasis in esophageal cancer and to test their value as predictive markers. EXPERIMENTAL DESIGN: We explored the gene expression profiles in cDNA array data of a 36-tissue training set of esophageal squamous cell carcinoma (ESCC) by using generalized linear model-based regression analysis and a feature subset selection algorithm. By applying the identified optimal feature sets (predictive gene sets), we trained and developed ensemble classifiers consisting of multiple probabilistic neural networks combined with AdaBoosting to predict tumor stages and lymph node metastasis. We validated the classifier abilities with 18 independent cases of ESCC. RESULTS: We identified 71 genes of 1289 cancer-related genes of which the expression correlated with tumor stages. Of the 71 genes, 47 significantly differed between the Tumor-Node-Metastasis pT1/2 and pT3/4 stages. Cell cycle regulators and transcriptional factors possibly promoting the growth of tumor cells were highly expressed in the early stages of ESCC, whereas adhesion molecules and extracellular matrix-related molecules possibly promoting invasiveness increased in the later stages. For lymph node metastasis, we identified 44 genes with predictive values, which included cell adhesion molecules and cell membrane receptors showing higher expression in node-positive cases and cell cycle regulators and intracellular signaling molecules showing higher expression in node-negative cases. The ensemble classifiers trained with the selected features predicted tumor stage and lymph node metastasis in the 18 validation cases with respective accuracies of 94.4% and 88.9%. This demonstrated the reproducibility and predictive value of the identified features. CONCLUSION: We suggest that these characteristic genes will provide useful information for understanding the malignant nature of ESCC as well as information useful for personalizing the treatments.

Algorithms↗
PubMed2004

Expression of pigment epithelium-derived factor decreases liver metastasis and correlates with favorable prognosis for patients with ductal pancreatic adenocarcinoma.

Pigment epithelium-derived factor (PEDF) is expressed in several normal organs and identified as an inhibitor of neovascularization. In the present study, we screened the expression of PEDF immunohistochemically and investigated its correlation with clinicopathological features in patients who underwent surgery for ductal pancreatic adenocarcinoma. Of the 80 patients, 22 cases (27.5%) were positive for PEDF. A significant association was found between the PEDF expression and low microvessel density (P = 0.0003). No correlation was found between PEDF expression and age, gender, depth of invasion, tumor diameter, lymphatic invasion, venous, invasion or histopathological grading. The patients in pathological stage II had a significantly higher incidence of PEDF-positive expression than those in pathological stage III or IVA (P = 0.0418). PEDF immunoreactivity was inversely associated with liver metastasis (P = 0.0422). The survival of patients that were PEDF positive was significantly longer than that of those with negative expression (P = 0.0026). Multivariate analysis using the Cox regression model indicated that PEDF-positive expression was an independent favorable prognostic factor (risk ratio, 0.394; P = 0.0016). We conclude that PEDF expression suggests a more favorable prognosis than in patients whose carcinomas lack PEDF expression.

Adult↗
PubMed2004

Genome-wide cDNA microarray analysis of gene expression profiles in pancreatic cancers using populations of tumor cells and normal ductal epithelial cells selected for purity by laser microdissection.

To characterize molecular mechanism involved in pancreatic carcinogenesis, we analysed gene-expression profiles of 18 pancreatic tumors using a cDNA microarray representing 23,040 genes. As pancreatic ductal adenocarcinomas usually contain a low proportion of cancer cells in the tumor mass, we prepared 95% pure populations of pancreatic cancer cells by means of laser microbeam microdissection, and compared their expression profiles to those of similarly purified, normal pancreatic ductal cells. We identified 260 genes that were commonly upregulated and 346 genes that were downregulated in pancreatic cancer cells. Because of the high degree of purity in the cell populations, a large proportion of genes that we detected as upregulated or downregulated in pancreatic cancers were different from those reported in previous studies. Comparison of clinicopathological parameters with the expression profiles indicated that altered expression of 76 genes was associated with lymph-node metastasis and that of 168 genes with liver metastasis. In addition, expression levels of 30 genes were related to the recurrence of disease. These genome-wide expression profiles should provide useful information for finding candidate genes whose products might serve as specific tumor markers and/or as molecular targets for treatment of patients with pancreatic cancer.

Epithelium↗
PubMed2004

Expression of N-acetylglucosaminyltransferase v is associated with prognosis and histology in non-small cell lung cancers.

PURPOSE: N-Acetylglucosaminyltransferase V (GnT-V), a key enzyme in the formation of branching of asparagine-linked oligosaccharides, is strongly linked to tumor invasion and metastasis of colon and breast cancers. However, GnT-V is expressed in many tissues, including normal lung. GnT-V expression has not been examined previously in human lung cancers. The objective of this study is to examine GnT-V expression in non-small cell lung cancers (NSCLCs) and to determine its relationship to biological and clinicopathological characteristics and prognosis. EXPERIMENTAL DESIGN: GnT-V expression was studied by immunohistochemistry in 217 surgically resected NSCLCs and analyzed statistically in relation to various characteristics. RESULTS: High GnT-V expression was found in 113 (52.1%) NSCLCs, and low GnT-V expression was found in 104 (47.9%) NSCLCs. Multivariate logistic regression analysis revealed a significant association between low GnT-V expression and squamous cell carcinomas, as compared with nonsquamous cell carcinomas (P = 0.02). Among biological characteristics of tumors, Ki-67 labeling index was higher in tumors with low GnT-V expression than in those with high GnT-V expression, although this difference was not statistically significant (P = 0.09). Patients with tumors having low GnT-V expression had significantly shorter survival time than patients with tumors having high GnT-V expression in 103 patients with pStage I NSCLCs (5-year survival rates, 49% and 86%, respectively; P = 0.0009), as well as in 59 patients with pStage I non-squamous cell carcinomas (5-year survival rates, 54% and 89%, respectively; P = 0.007). Low GnT-V expression was a significant unfavorable prognostic factor in pStage I NSCLCs (hazard ratio, 2.86; P = 0.002) and in pStage I nonsquamous cell carcinomas (hazard ratio, 3.02; P = 0.02). Furthermore, beta1-6 branching of asparagine-linked oligosaccharides, which are products of GnT-V, were increased highly or moderately in 8 of 10 tumors with high GnT-V expression, as judged by leukoagglutinating phytohemagglutinin staining. CONCLUSIONS: GnT-V expression is associated with histology in NSCLCs. Low GnT-V expression is associated with shorter survival and poor prognosis in pStage I overall NSCLCs and non-squamous cell carcinomas.

Aged↗
PubMed2004

Evaluation of 18F-2-deoxy-2-fluoro-D-glucose positron emission tomography for gastric cancer.

Positron emission tomography (PET) with (18)F-2-deoxy-2-fluoro-D-glucose (FDG) has been investigated as a means of detecting certain primary tumors and their metastatic disease in recent years. The aim of this study was to compare the performance of FDG-PET and operative assessment with formal pathologic staging. Altogether, 85 patients had undergone surgical treatment for gastric cancer with curative intent, with FDG-PET preoperatively. The results using FDG-PET were compared with those using computed tomography (CT); they were also correlated with the pathologic findings. For quantitative analysis, the regional tumor uptake was measured by the standard uptake value (SUV) using a region of interest technique. Using FDG-PET, the primary tumor was visualized in 75.2% of patients. A comparison of the FDG uptake and the clinicopathologic findings showed that there was a significant association between FDG uptake and the depth of invasion, the size of the tumor, and lymph node metastasis. FDG-PET scans had less accuracy for diagnosing locoregional lymph nodes than CT because of a significant lack of sensitivity (23.3% vs. 65.0%). The survival rate for patients with high FDG uptake (SUV > 4) was significantly lower than that for those with low FDG uptake (SUV < 4) ( p < 0.05). FDG-PET was successful in detecting the primary gastric cancer lesion but not for finding early-stage gastric cancers. Detection of nodal metastasis also was not possible by FDG-PET. However, FDG-PET appears to provide important additional information concerning the aggressiveness of the tumor and the prognosis in patients with gastric cancer.

Adult↗
PubMed2004

Generation and targeting of human tumor-specific Tc1 and Th1 cells transduced with a lentivirus containing a chimeric immunoglobulin T-cell receptor.

CD4+ Th cells, in particular IFN-gamma-producing Th1 cells, play a critical role in the activation and maintenance of Tc1 cells that are essential for tumor eradication. Here, we report the generation of artificial tumor-specific Th1 and Tc1 cells from nonspecifically activated T cells using a lentiviral transduction system. Anti-CD3-activated T cells from healthy human donors were transduced with a lentivirus containing a chimeric immunoglobulin T-cell receptor gene composed of single-chain variable fragments derived from an anticarcinoembryonic antigen (CEA)-specific monoclonal antibody fused to an intracellular signaling domain derived from the cytoplasmic portions of membrane-bound CD28 and CD3zeta. These artificial tumor-specific Tc1 and Th1 cells, termed Tc1- and Th1-T bodies, respectively, could be targeted to CEA+ tumor cells independently of MHC restriction. Specifically, Tc1-T bodies demonstrated high cytotoxicity and produced IFN-gamma in response to CEA+ tumor cell lines but not CEA- tumors. Although Th1-T bodies exhibited low cytotoxicity, they secreted high levels of IFN-gamma and interleukin-2 in response to CEA+ tumor cells. Such CEA+ tumor-specific activation was not observed in mock gene-transduced nonspecific Tc1 and Th1 cells. Moreover, Tc1- and Th1-T bodies exhibited strong antitumor activities against CEA+ human lung cancer cells implanted into RAG2(-/-) mice. Furthermore, combined therapy with Tc1- and Th1-T bodies resulted in enhanced antitumor activities in vivo. Taken together, our findings demonstrate that Tc1- and Th1-T bodies represent a promising alternative to current methods for the development of effective adoptive immunotherapies.

Animals↗