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T Kikuchi

Publications and source records attributed to T Kikuchi.

At least 91 records · Page 5Linked to original sources
PubMed2001

[Prediction of the need for mechanical ventilation after transsternal thymectomy in patients with myasthenia gravis].

Between June 1992 and May 2000, transsternal extended thymectomy was performed for 70 patients with myasthenia gravis in our hospital. We were able to evaluate 64 of them in terms of prediction of the need for postoperative mechanical ventilation using the score systems reported by Leventhal et al., Kimura et al. and the criteria of Adachi et al.. For these systems, the rates of agreement between predictions and results were 85.9%, 82.8%, and 64.1%, respectively. The two former systems had some false negative cases (i.e., they predicted that ventilation would not be needed when in fact it was), but the last one gave no false negatives. We recommend Adachi's criteria for clinical safety. In our cases the patients whose value of %VC multiplied by FEV1.0% was less than 7,000 (Adachi's criterion is less in 8,300), especially, needed careful management with regard to respiratory crisis.

Adolescent↗
PubMed2001

Hyperactivity of 99mTc-HMPAO within 6 hours in patients with acute ischemic stroke.

UNLABELLED: Intraarterial thrombolytic therapy has been used recently for treatment of acute ischemic stroke within 6 h after onset. Although hypoactivity of 99mTc-hexamethylpropyleneamine oxime (HMPAO) in stroke has been well documented, hyperactivity of HMPAO has not been evaluated in sufficient detail. The purpose of this study was to evaluate the incidence and clinical importance of hyperactivity of HMPAO in management of patients with acute ischemic stroke. METHODS: We retrospectively investigated HMPAO SPECT in 90 patients with acute ischemic stroke within 6 h after onset. The lesion-to-contralateral radioactivity ratios (L/Cs) were calculated on the SPECT images before treatment and were compared with the imaging results of CT or MRI (or both). RESULTS: Hyperactivity of HMPAO, accompanied by surrounding hypoactivity, was observed in 6 of 90 patients (7%) within 6 h after onset. The L/Cs ranged from 1.17 to 2.95. Two patients showed hyperactivity in the cortex and the other 4 patients showed hyperactivity in the basal ganglia. Angiography confirmed spontaneous recanalization of occluded vessels in accordance with the area of hyperactivity. In both patients with cortical hyperactivity, cerebral infarctions were revealed on follow-up CT; in 1 patient, hemorrhagic transformation developed after intraarterial thrombolytic therapy. In 3 of the 4 patients with hyperactivity in the basal ganglia, follow-up CT showed no infarction in the surrounding hypoperfused cortex (selective intraarterial thrombolytic therapy was performed on 2 patients), although various degrees of infarction were observed in the basal ganglia. Obvious infarctions developed in the basal ganglia and the cortex of the other patient. CONCLUSION: Hyperactivity of HMPAO could be seen in the basal ganglia and the cortex within 6 h after onset, reflecting spontaneous recanalization. The areas of hyperactivity may develop infarctions, whereas the accompanying areas of hypoactivity could be rescued by selective intraarterial thrombolytic therapy.

Acute Disease↗
PubMed2001

[Case report of scimitar syndrome in infancy: intracardiac repair after coil embolization of systemic arterial supply to sequestered lung].

A 10-month-old girl was diagnosed with atrial septal defect and pulmonary sequestration and scimitar syndrome. Cardiac catheterization revealed severe pulmonary hypertension, with systemic pulmonary artery pressure 97 mmHg, pulmonary resistance 10.3 U, and Qp/Qs 0.45. Systemic pulmonary artery pressure was decreased from 108 to 75 mmHg by oxygenation. We performed coil embolization of the systemic artery and repair of the partial anomalous pulmonary venous return, division and reimplantation of the anomalous vein into the right atrium, and a patch was inserted to redirect flow to the left atrium. The severe pulmonary hypertension was improved and echocardiography showed systemic pulmonary artery pressure of 45 mmHg. The postoperative hemodynamic and respiratory condition was satisfactory.

Bronchopulmonary Sequestration↗
PubMed2001

Fractal analysis of cerebral blood flow distribution in Alzheimer's disease.

UNLABELLED: This study describes a method for quantifying cerebral blood flow (CBF) distribution in Alzheimer's disease (AD) from SPECT images obtained with (99m)Tc-hexamethylpropyleneamine oxime (HMPAO) by 3-dimensional fractal analysis (3D-FA). METHODS: HMPAO SPECT was performed on 68 patients with probable AD and 14 healthy control subjects. We delineated the CBF images using 4 cutoff levels (35%, 40%, 45%, and 50% of the maximal voxel radioactivity) and measured the total number of voxels in the areas surrounded by the contours obtained with each cutoff level. We calculated fractal dimensions from the relationship between the total number of voxels and the cutoff levels transformed into natural logarithms. RESULTS: The fractal dimensions (mean +/- SD) for patients with probable AD and healthy subjects were 0.74 +/- 0.33 and 0.52 +/- 0.09, respectively. A significant difference in the fractal dimension was found between groups (P = 0.001). Statistically significant correlations were obtained between the fractal dimension and the Mini-Mental State Examination score (r = -0.598; P < 0.0001) and between the fractal dimension and the AD Assessment Scale (r = 0.670; P < 0.0001). The fractal dimensions for subjects with clinical dementia rates (CDRs) of 0, 1, 2, and 3 were 0.52 +/- 0.09, 0.63 +/- 0.21, 0.77 +/- 0.23 (P < 0.05 vs. the group with a CDR of 1), and 1.43 +/- 0.49 (P < 0.0001 vs. the group with a CDR of 2), respectively. CONCLUSION: Quantification of CBF distribution on SPECT images in AD was possible using 3D-FA. The fractal dimension was well correlated with the cognitive impairment, as assessed in neuropsychologic tests. 3D-FA may be a useful method for objectively evaluating the progression of AD.

Aged↗
PubMed2000

Production of luciferase-magnetic particle complex by recombinant Magnetospirillum sp. AMB-1.

Luciferase-bacterial magnetic particle (BMP) complexes were produced by recombinant Magnetospirillum sp. AMB-1. We constructed plasmids pKML and pNELM, respectively, by fusing luc to the 5' and 3' terminal of magA, encoding an integral iron translocating protein situated in the BMP membrane, of AMB-1. In addition, we produced bifunctional active-fusion proteins on BMPs by using a plasmid pAcML. In this plasmid, acetate kinase and luciferase genes were fused to the N-terminus and the C-terminus of MagA, respectively. Bacterial magnetic particles isolated from transconjugants for pKML, pNELM and pAcML exhibited luciferase activity. Bacterial magnetic particles isolated from transconjugants for pAcML also exhibited acetate kinase activity. Fed-batch culture of pKML transconjugant yielded 2.6 mg BMPs per liter of culture, and 95% conversion of iron into magnetite was obtained, at a nitrate concentration of 1.4 mM. Continuous feeding of iron as ferric quinate significantly enhanced growth and total magnetic production. Final cell concentration of 1.8 x 10(9) cells/mL and 6 mg per liter of culture was obtained. Magnetite production by fed-batch culture of AMB-1 was about 3 times that obtained by batch culture. There were no significant differences in BMPs yield between recombinant AMB-1 cultivated by fed-batch culture and wild type of AMB-1.

Acetate Kinase↗
PubMed2000

Cutting edge: naturally occurring soluble form of mouse Toll-like receptor 4 inhibits lipopolysaccharide signaling.

Toll-like receptors (TLRs) are a family of proteins playing important roles in host defense. Mice defective of functional TLR4 are hyporesponsive to LPS, suggesting that TLR4 is essential for LPS signaling. Here we report the cloning of an alternatively spliced mouse TLR4 (mTLR4) mRNA. The additional exon exists between the second and third exon of the reported mTLR4 gene and contains an in-frame stop codon. The alternatively spliced mRNA encodes 86 aa of the reported mTLR4 and an additional 36 aa. This alternatively spliced mTLR4 mRNA expressed a partially secretary 20-kDa protein, which we named soluble mTLR4 (smTLR4). In a mouse macrophage cell line, the exogenously expressed smTLR4 significantly inhibited LPS-mediated TNF-alpha production and NF-kappaB activation. Additionally, in mouse macrophages, LPS increased the mRNA for smTLR4. Taken together, our results indicate that smTLR4 may function as a feedback mechanism to inhibit the excessive LPS responses in mouse macrophages.

Alternative Splicing↗
PubMed2000

Caveolin-3 deficiency causes muscle degeneration in mice.

Caveolin-3 is a muscle-specific protein integrated in the caveolae, which are small invaginations of the plasma membrane. Mutations of the caveolin-3 gene, localized at 3p25, have been reported to be involved in the pathogenesis of limb-girdle muscular dystrophy (LGMD1C or caveolinopathy) with mild clinical symptoms, inherited through an autosomal dominant form of genetic transmission. To elucidate the pathogenetic mechanism, we developed caveolin-3-deficient mice for use as animal models of caveolinopathy. Caveolin-3 mRNA and its protein were absent in homozygous mutant mice. In heterozygous mutant mice, both the mRNA and its protein were normal in size, but their amounts were reduced by about half. The density of caveolae in skeletal muscle plasma membrane was roughly proportional to the amount of caveolin-3. In homozygous mutant mice, muscle degeneration was recognized in soleus muscle at 8 weeks of age and in the diaphragm from 8 to 30 weeks, although there was no difference in growth and movement between wild-type and mutant mice. No apparent muscle degeneration was observed in heterozygous mutant mice, indicating that pathological changes caused by caveolin-3 gene disruption were inherited through the recessive form of genetic transmission.

Animals↗
PubMed2000

Production efficiency of Japanese black calves by transfer of bovine embryos produced in vitro.

The objective of this study was to examine the production efficiency of Japanese Black beef calves after transfer of bovine embryos derived from an in vitro procedure. In vitro-produced (IVP) embryos were obtained from in vitro maturation and fertilization and in vitro development by co-culture with cumulus cells until 7 or 8 days after insemination. In vivo-developed (IVD) embryos from superovulated Japanese Black heifers and cows 7 days after artificial insemination were used as a control group. Bovine embryos were transferred nonsurgically to recipient cows on Day 7 +/- 1 of the estrous cycle. Pregnancy was diagnosed by palpation per rectum at Day 60 to 70 after estrus. Pregnancy, abortion, perinatal accident and birth rates were examined according to the origin of embryos (IVP or IVD), the number of transferred embryos (single or twin) and the storage status (fresh or frozen-thawed). In Experiment 1, production efficiency by twin transfer of fresh IVP embryos was examined. Higher pregnancy rates (52 1% vs 42 9%, P < 0.05) and birth rates (47.0% vs. 33.0%, P < 0.05) were obtained by twin transfer than by single transfer of fresh IVP embryos. Thus, the twin transfer of fresh IVP embryos was effective for production of calves, although the birth rates for single and twin transfers of fresh IVD embryos were still higher (55.5% and 76.1%, P < 0.05). But the abortion and perinatal accident rates for twin transfer of fresh IVP embryos were also significantly greater than those for single and twin transfer of fresh IVD embryos (P < 0.05). In Experiment 2, production efficiency by twin transfer of frozen-thawed IVP embryos was examined. Either single or twin transfer of frozen-thawed IVP embryos resulted in a similar pregnancy rate (41.3% vs. 46.7%, P > 0.05) and birth rate (34.1% vs. 41.1%, P>0.05). Thus, in combination with frozen-thawed IVP embryos, the twin transfer did not enhance production efficiency. In conclusion, Japanese Black beef calves could effectively produce calves by twin transfer to Holstein recipients when using fresh IVP embryos, and by single transfer when using frozen-thawed IVP embryos.

Abortion, Spontaneous↗
PubMed2000

Birth weight and birth rate of heavy calves conceived by transfer of in vitro or in vivo produced bovine embryos.

The aim of this study was to evaluate the difference in birth weight and gestation length between Japanese Black calves obtained from transfer of bovine embryos produced in vitro (IVP) and those developed in vivo (IVD). An additional objective was to clarify the sire effect on birth weight and gestation length and to examine the birth rate of heavier calves. Two Japanese Black bulls breed at our experimental station were used as a semen source for production of IVP and IVD embryos. Thirty-eight Japanese Black heifers and cows of various genetic backgrounds were used as embryo donors for IVD embryos. Ovaries for IVP embryos were collected at random at a local slaughterhouse from Japanese Black cattle of various genetic backgrounds. IVP embryos were produced using co-culturing with cumulus cells in 5% CS+TCM 199. Both the IVD and IVP embryos were transferred non-surgically to Holstein recipients on day 7+/-1 of estrous cycle. In this study, the birth weights and gestation lengths of half-sib single calves for bull A and B were analyzed. The numbers of single calves born by transfer of IVP and IVD embryos for bull A and B were 133 and 121, 243 and 465, respectively. The birth weight of the IVP calves was significantly higher (P<0.01) than that of the IVD (bull A: 31.0+/-0.4 kg versus 27.2+/-0.4 kg and bull B: 29.9+/-0.6 kg versus 26.6+/-0.2 kg). Gestation length of the IVP calves for bull A was significantly longer (P<0.01) than that of the IVD (291.9+/-0.9 days versus 283.6+/-0.5 days). However, for bull B, there were no differences in gestation length between the IVP and IVD calves (285.9+/-0.7 days versus 286.2+/-0.3 days). These results clearly indicated that IVP calves had heavier birth weights than IVD calves but that the average gestation length of IVP calves was not always longer than that of IVD calves. Furthermore, the birth rate of heavier calves and the incidence of stillbirth and perinatal mortality up to 48 h post partum in IVP calves (bull A: 11.3%, bull B: 7.8%) were greater (P<0.05) than those in IVD calves from both bulls (bull A: 4.1%, bull B: 3.7%).

Animals↗
PubMed2000

Caspases that are activated during generation of nuclear polyglutamine aggregates are necessary for DNA fragmentation but not sufficient for cell death.

Truncated polypeptides containing expanded polyglutamine (polyQ) stretches tend to form cytoplasmic or nuclear aggregates in cultured cells, leading to cell death. Although it has been shown recently that caspase-8 coaggregates with polyQ and is activated during polyQ-mediated cell death, little is known of the location and timing of caspase-8 activation by nuclear polyQ aggregates. Also, the relationship between nuclear polyQ aggregate-mediated cell death and activation of other caspases is unclear. In P19 embryonal carcinoma (EC) cells, which can be made to differentiate into neuronal cells, polyQ72 repeats preferentially aggregate in the nucleus. Nuclear aggregates of polyQ72 induced P19 EC cell death, with a high frequency of cells exhibiting morphology characteristic of apoptosis (i.e., roundness, cell shrinkage, chromatin condensation) and DNA fragmentation. In the present study, we used antisera that specifically recognized the active forms of caspase-8, -3, and -9 but not their proforms, and showed that only caspase-8 and -3 were activated during the generation of polyQ72 aggregates in P19 EC cell nuclei. Furthermore, we showed that the caspase inhibitor z-VAD-fmk inhibited DNA fragmentation, but only partially inhibited the appearance of apoptotic morphology. Thus, caspase activation, including caspase-8 and -3, is necessary for polyQ-mediated DNA fragmentation but not sufficient for polyQ-mediated cell death in P19 EC cells.

Apoptosis↗
PubMed2000

Tumor regression induced by intratumor administration of adenovirus vector expressing CD40 ligand and naive dendritic cells.

We have previously shown that in vivo genetic modification of tumors with an adenovirus (Ad) vector engineered to express CD40 ligand (AdmCD40L) induces tumor-specific CTLs and suppresses tumor growth in vivo. In the present study, we investigate the hypothesis that this treatment can be made more efficient with 10(2)-fold less Ad vector by also administering bone marrow-generated dendritic cells (DCs) to the tumor. Using AdmCD40L and the number of DCs that alone had no effect on tumor growth, the data show that the growth of CT26 (colon adenocarcinoma; H-2d) and B16 (melanoma; H-2b) murine s.c. tumors is significantly suppressed by direct administration of DCs into s.c. established tumors that had been pretreated with AdmCD40L 2 days previously. The antitumor effect produced by the combination therapy AdmCD40L + DCs correlated with in vivo priming of tumor-specific CTLs. The antitumor cell-mediated immunity was transferable to naive mice by spleen cells from AdmCD40L + DC-treated animals. The interactions between CD40L and CD40 within treated tumors were critical because tumor suppression was abrogated by coadministration to the tumors of neutralizing monoclonal antibody against CD40L along with the DCs. Finally, in vivo depletion and knockout mice experiments demonstrated that tumor regression produced by this combination therapy depends on CD8+ T cells, but not on CD4+ T cells. These findings should be useful in designing strategies for use of DCs and AdmCD40L in cancer immunotherapy.

Adenocarcinoma↗
PubMed2000

Frequent hypermethylation of CpG islands and loss of expression of the 14-3-3 sigma gene in human hepatocellular carcinoma.

The 14-3-3 sigma gene has been implicated in G2/M cell cycle arrest by p53. Frequent inactivation of the 14-3-3 sigma gene by hypermethylation of CpG islands has recently been reported in human breast carcinoma. The aim of this study was to examine the methylation status of CpG islands of the 14-3-3 sigma gene in hepatocellular carcinoma (HCC). The methylation status of the 14-3-3 sigma gene was evaluated in four normal liver tissues and 19 paired specimens of carcinoma and adjacent non-tumorous liver tissues using bisulfite-single strand conformation polymorphism (bisulfite-SSCP), a combination of sodium bisulfite modification and fluorescence-based polymerase chain reaction (PCR)-SSCP. The 14-3-3 sigma protein expression was examined by immunohistochemical staining. Hypermethylation of CpG islands of the 14-3-3 sigma gene was detected in 89% (17/19) of the HCC tissues but not in any of the four normal liver tissues. All of the 14 methylation-positive HCC samples analysed by immunohistochemistry showed loss of 14-3-3 sigma expression, while both of the methylation-negative HCC samples retained the expression, and a significant correlation was found between methylation and loss of expression. Lower levels of methylation were detected in adjacent non-tumorous liver tissues (6/16 in cirrhotic tissues and 1/3 in chronic hepatitis tissues), but the 14-3-3 sigma expression was retained in all of these tissues. In a methylation-positive HCC cell line, HLE, 5-aza-2'-deoxycytidine (5-aza-dC)-induced demethylation of CpG islands led to reactivation of gene expression, indicating that hypermethylation plays a causal role in inactivation of the 14-3-3 sigma gene in HCC. Hypermethylation and the resulting loss of expression of the 14-3-3 sigma gene corresponds to one of the most common abnormalities reported to date in HCC, suggesting their crucial role in the development and/or progression of HCC.

14-3-3 Proteins↗
PubMed2000

Blockade of T lymphocyte costimulation with cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4Ig) reverses the cellular pathology of psoriatic plaques, including the activation of keratinocytes, dendritic cells, and endothelial cells.

Efficient T cell activation is dependent on the intimate contact between antigen-presenting cells (APCs) and T cells. The engagement of the B7 family of molecules on APCs with CD28 and CD152 (cytotoxic T lymphocyte-associated antigen 4 [CTLA-4]) receptors on T cells delivers costimulatory signal(s) important in T cell activation. We investigated the dependence of pathologic cellular activation in psoriatic plaques on B7-mediated T cell costimulation. Patients with psoriasis vulgaris received four intravenous infusions of the soluble chimeric protein CTLA4Ig (BMS-188667) in a 26-wk, phase I, open label dose escalation study. Clinical improvement was associated with reduced cellular activation of lesional T cells, keratinocytes, dendritic cells (DCs), and vascular endothelium. Expression of CD40, CD54, and major histocompatibility complex (MHC) class II HLA-DR antigens by lesional keratinocytes was markedly reduced in serial biopsy specimens. Concurrent reductions in B7-1 (CD80), B7-2 (CD86), CD40, MHC class II, CD83, DC-lysosomal-associated membrane glycoprotein (DC-LAMP), and CD11c expression were detected on lesional DCs, which also decreased in number within lesional biopsies. Skin explant experiments suggested that these alterations in activated or mature DCs were not the result of direct toxicity of CTLA4Ig for DCs. Decreased lesional vascular ectasia and tortuosity were also observed and were accompanied by reduced presence of E-selectin, P-selectin, and CD54 on vascular endothelium. This study highlights the critical and proximal role of T cell activation through the B7-CD28/CD152 costimulatory pathway in maintaining the pathology of psoriasis, including the newly recognized accumulation of mature DCs in the epidermis.

Abatacept↗
PubMed2000

Pulmonary vascular disease in Down's syndrome with complete atrioventricular septal defect.

We sought to determine the predisposing factors of pulmonary vascular disease (PVD) in complete atrioventricular septal defect. Down's syndrome is considered a risk factor for PVD, but the progression of PVD differs in each case. Morphometric analysis in autopsied hearts showed that Rastelli type A morphology had a narrower left ventricular outlet and a wider right ventricular outlet than did type C. In 81 consecutive patients with Down's syndrome who underwent cardiac catheterization, we estimated the following variables: Rastelli subtypes, pulmonary vascular resistance, pulmonary-to-systemic flow ratio, patients' age, and operative outcome. The hemodynamic variables in those <1 year old did not differ between the groups with type A and type C. However, all 5 patients with fatal pulmonary hypertension in early infancy had type A morphology. The lung histology revealed that 3 of these patients already had irreversible PVD. At >/=1 year old, those with type A showed a significantly higher pulmonary vascular resistance (p <0.001) and a lower pulmonary to systemic flow ratio (p <0.05) than did those <1 year old. In contrast, neither of these variables in the type C group differed between those >/=1 and <1 year old. Moreover, those with type A had a greater risk of being contraindicated for surgical repair (p <0.05). We suspect, therefore, that type A morphology is an independent risk factor for PVD in those with Down's syndrome associated with this anomaly. This hemodynamic influence could become obvious once patients are >/=1 year old. It may also sometimes result in irreversible PVD even in early infancy.

Adolescent↗
PubMed2000

Inactivation of the 14-3-3 sigma gene is associated with 5' CpG island hypermethylation in human cancers.

The cell cycle checkpoint plays an important role in maintaining the integrity of cells. Recently, one of the 14-3-3 protein family members, 14-3-3sigma, was shown to be regulated by p53 and to play a role in the G2-M-phase checkpoint. To determine whether 14-3-3sigma is inactivated in human cancers, the methylation status of the 5' region of 14-3-3sigma was investigated in a series of gastric, colorectal, and hepatocellular cancer cell lines. Of 22 cell lines examined, 6 showed aberrant methylation. The methylation status of 14-3-3sigma was found to be correlated with loss of expression, which was restored by 5-aza-2'-deoxycytidine treatment. Furthermore, normal G2 arrest after DNA damage was not demonstrated in the cell lines with methylation. In primary gastric cancers, 14-3-3sigma hypermethylation was observed frequently in 26 of 60 (43%) cases and observed more frequently in poorly differentiated adenocarcinomas (P = 0.0017). Our findings suggest that 14-3-3sigma is inactivated by aberrant methylation of the 5' region in various human cancers and that it might play an important role in the development of undifferentiated gastric cancers.

14-3-3 Proteins↗
PubMed2000

Expression of connexin 31 in the developing mouse cochlea.

Connexin 31 (Cx31) mutations cause an autosomal dominant form of high-frequency hearing loss. The immunohistochemical localization of Cx31 in mouse cochlea was studied at different ages between 0 and 60 days after birth (DAB). Cx31-like immunoreactivity was detected in fibrocytes of spiral ligament and spiral limbus at 12 DAB, gradually enhanced with the increase of age and reached the adult pattern on 60 DAB. Immunoreactivity decreased gradually from the basal to apical turn in all developmental stages. The mRNA of Cx31 was also identified by RT-PCR. The distribution of Cx31 and connexin 26 were obviously different in the developing mouse cochlea. The expression and distribution of Cx31 in the development may explain the progressive hearing loss in human Cx31 mutations.

Age Factors↗
PubMed2000

Dendritic cells modified to express CD40 ligand elicit therapeutic immunity against preexisting murine tumors.

CD40 ligand (CD40L) is essential for the initiation of antigen-specific T-cell responses. This study is based on the hypothesis that dendritic cells (DCs) genetically modified ex vivo to express CD40L will enhance in vivo presentation of tumor antigen to the cellular immune system with consequent induction of antitumor immunity to suppress tumor growth. To examine this concept, subcutaneous murine tumors were injected with bone marrow-derived DCs that had been modified in vitro with an adenovirus (Ad) vector expressing murine CD40L (AdmCD40L). In B16 (H-2(b), melanoma) and CT26 (H-2(d), colon cancer) murine models, intratumoral injection of 2 x 10(6) AdmCD40L-modified DCs (CD40L-DCs) to established (day 8) subcutaneous tumors resulted in sustained tumor regression and survival advantage. This antitumor effect was sustained when the number of CD40L-DCs were reduced 10-fold to 2 x 10(5). Analysis of spleens from CD40L-DC-treated animals demonstrated that CD40L-DCs injected into the subcutaneous CT26 flank tumors migrated to the spleen, resulting in activation of immune-relevant processes. Consistent with this concept, intratumoral administration of CD40L-DCs elicited tumor-specific cytotoxic T-lymphocyte responses, and the transfer of spleen cells from CD40L-DC-treated mice efficiently protected naive mice against a subsequent tumor challenge. In a distant 2-tumor model of metastatic disease, an untreated B16 tumor in the right flank regressed in parallel with a left B16 tumor treated with direct injection of CD40L-DCs. These results support the concept that genetic modification of DCs with a recombinant CD40L adenovirus vector may be a useful strategy for directly activating DCs for cancer immunotherapy.

Adenocarcinoma↗