Search PubMed⌕ Search

Biomedical subjects

M Adachi

Publications and source records attributed to M Adachi.

At least 37 records · Page 2Linked to original sources
PubMed2003

Cellulose acetate beads induce release of interleukin-1 receptor antagonist, but not tumour necrosis factor-alpha or interleukin-1beta in human peripheral blood.

OBJECTIVE: Dramatic improvements in clinical symptoms of rheumatoid arthritis and ulcerative colitis were observed after patients received granulocyte and monocyte adsorptive apheresis with a column containing cellulose acetate (CA) beads as adsorptive carriers. This study was to investigate the effect of CA beads on the generation of anti-inflammatory and pro-inflammatory cytokines in human blood. MATERIALS AND METHODS: We incubated human whole blood with CA beads at 37 degrees C for up to 2 h and measured tumour necrosis factor-alpha (TNF-alpha) interleukin-1beta (IL-1beta) and IL-1 receptor antagonist (IL-1ra) produced by leucocytes. IL-1ra was also measured at the inflow and outflow of a column containing CA beads as leucocyte adsorptive carriers for the treatment of patients with ulcerative colitis. RESULTS: CA beads induced significant release of IL-1ra from leucocytes, but not TNF-alpha or IL-1beta. In contrast, all three cytokines were released when leucocytes were stimulated with lipopolysaccharide. IL-1ra was also markedly elevated in the outflow of the leucocyte apheresis column. CONCLUSIONS: These results indicate that CA beads selectively induce IL-1ra release from leucocytes which should contribute to the anti-inflammatory effect of granulocyte and monocyte adsorptive apheresis with CA beads as apheresis carriers.

Adolescent↗
PubMed2003

Final height and pubertal growth in Japanese patients with congenital hypothyroidism detected by neonatal screening.

AIM: To investigate the final adult heights and pubertal growth patterns in Japanese patients with congenital hypothyroidism (CH) detected by neonatal screening. METHODS: A retrospective chart review was conducted of female patients >15 y of age (n = 18) and male patients >18 y of age (n = 9), who were detected by neonatal screening and kept on continuous thyroid hormone replacement therapy. Final height standard deviation scores (FHSDS) and target height standard deviation scores (THSDS) were determined. Parameters characterizing the pubertal growth process (such as age at onset of pubertal growth spurt and age at peak pubertal growth) were obtained from each patient's growth rate chart. Menarchial age was determined in each female patient by reviewing the medical record. The impact on FHSDS of the etiology of CH, the severity of CH, the time of initiation of therapy and the adequacy of treatment during the first year of life was assessed. RESULTS: All patients had received initial thyroid hormone treatment no later than 50 d of age, and had reached their final height. The mean FHSDS for female and male patients were +0.17 +/- 0.99 and -0.03 +/- 0.99, respectively. The mean FHSDS-THSDS for female and male patients was +0.09 +/- 0.77 and -0.19 +/- 0.53, respectively. No difference was seen in pubertal growth parameters for either gender compared with that of the reference population, except for a greater peak height velocity and pubertal height gain in male patients. The mean menarchial age was identical to that of the reference population. No significant relationship was found between the FHSDS and any of the factors investigated. CONCLUSION: The adult height of patients with CH detected by neonatal screening was equivalent to that of the reference population and their target height. As long as early intervention and satisfactory management are ensured, severe CH does not appear to reduce final adult height.

Adolescent↗
PubMed2003

Cough receptor sensitivity to capsaicin does not change after allergen bronchoprovocation in allergic asthma.

BACKGROUND: The relationship between cough receptor sensitivity and eosinophilic inflammation of the airway in patients with asthma remains unclear. METHODS: Eighteen patients with asthma sensitised to house dust mite (HDM) were enrolled in a randomised parallel group study. Patients with asthma whose main symptom was cough were not enrolled in the study. Half the patients were randomly assigned to inhale saline and the other half to inhale HDM allergen. Cough receptor sensitivity to capsaicin, airway responsiveness to histamine, and sputum eosinophils analysed with hypertonic saline inhalation were investigated before and 24 hours after saline or HDM allergen bronchoprovocation. RESULTS: Patients inhaling saline showed no significant changes in sputum eosinophils (from 7.87% (95% confidence interval (CI) 5.08 to 12.19) to 8.60% (95% CI 3.03 to 14.18); p=0.97), airway responsiveness to histamine (from 726.68 micro g/ml (95% CI 251.90 to 2096.36) to 773.01 micro g/ml (95% CI 251.36 to 2377.23); p=0.96), or capsaicin sensitivity (from 7.23 micro M (95% CI 2.45 to 21.31) to 7.24 micro M (95% CI 2.46 to 21.31); p=0.96). Early asthmatic response was induced in all patients, and late asthmatic response was observed in six of nine patients inhaling HDM allergen. Although there were significant increases in sputum eosinophils (from 9.83% (95% CI 6.78 to 14.27) to 21.00% (95% CI 13.85 to 28.15); p<0.01) and airway responsiveness to histamine (from 784.16 micro g/ml (95% CI 318.24 to 1932.24) to 377.81 micro g/ml (95% CI 118.43 to 1205.24); p<0.05) 24 hours after HDM allergen inhalation compared with baseline levels, capsaicin sensitivity did not change significantly (from 5.75 micro M (95% CI 1.91 to 17.30) to 6.20 micro M (95% CI 2.21 to 17.38); p=0.77). CONCLUSIONS: These findings suggest that cough receptor sensitivity to capsaicin is not associated with eosinophilic inflammation of the airway in patients with allergic asthma whose main symptoms are wheezing and dyspnoea but not cough.

Adult↗
PubMed2003

Front-loading of Groningen voice prosthesis in alaryngeal patients requiring prosthetic replacement.

The Groningen voice prosthesis can be successfully replaced using the back-loading system. We have attempted to minimize patient stress by developing a front-loading system that does not require insertion of the introducer via the tracheo-oesophageal shunt to the oral cavity or the mesopharyngeal anaesthetization regularly used with the back-loading system. Using our front-loading system, the existing prosthesis is removed, then the posterior portion of the replacement Groningen prosthesis is grasped by a pair of nasal forceps with a small jaw to make an acute angle and inserted into the oesophageal cavity through the shunt at a stroke. All 20 patients who underwent forward-loading replacement of a Groningen (n = 17) or Blom-Singer (n = 3) valve with a Groningen valve tolerated the procedure well and experienced no complications except, in some cases, for minor bleeding just after insertion of the prosthesis. The procedure was completed within 30 seconds.

Humans↗
PubMed2002

Impaired 2',3'-dideoxy-3'-thiacytidine accumulation in T-lymphoblastoid cells as a mechanism of acquired resistance independent of multidrug resistant protein 4 with a possible role for ATP-binding cassette C11.

Cellular factors may contribute to the decreased efficacy of chemotherapy in HIV infection. Indeed, prolonged treatment with nucleoside analogues, such as azidothymidine (AZT), 2',3'-deoxycytidine or 9-(2-phosphonylmethoxyethyl)adenine, induces cellular resistance. We have developed a human T lymphoblastoid cell line (CEM 3TC) that is selectively resistant to the antiproliferative effect of 2',3'-dideoxy-3'-thiacytidine (3TC) because the CEM 3TC cells were equally sensitive to AZT, as well as the antimitotic agent, vinblastine. The anti-retroviral activity of 3TC against HIV-1 was also severely impaired in the CEM 3TC cells. Despite similar deoxycytidine kinase activity and unchanged uptake of nucleosides such as AZT and 2'-deoxycytidine, CEM 3TC had profoundly impaired 3TC accumulation. Further studies indicated that CEM 3TC retained much less 3TC. However, despite a small overexpression of multidrug resistance protein (MRP) 4, additional studies with cells specifically engineered to overexpress MRP4 demonstrated there was no impact on either 3TC accumulation or efflux. Finally, an increased expression of the MRP5 homologue, ATP-binding cassette C11 (ABCC11) was observed in the CEM 3TC cells. We speculate that the decreased 3TC accumulation in the CEM 3TC might be due to the upregulation of ABCC11.

ATP-Binding Cassette Transporters↗
PubMed2002

MR and CT findings of craniopharyngioma during and after radiation therapy.

Long-term changes in craniopharyngioma treated with radiation therapy (RT) were investigated by computed tomography (CT) and/ or magnetic resonance (MR) imaging. Eight patients with craniopharyngioma were treated with incomplete resection or conservative surgical intervention followed by postoperative RT. The periods of tumor shrinkage were often long and varied (range: 6-68 months, mean: 29.1 months). Temporary enlargement of the solid component of a tumor usually occurs during RT and does not represent tumor progression. Cystic enlargement also occurs sometimes comparatively early after RT, and enlarged cysts often shrink with no treatment or with conservative treatment. These changes should be differentiated from tumor recurrence, with careful follow-up. After shrinkage, small solid or cystic nodules enhanced with contrast medium often remain. Long-term follow-up is necessary to differentiate uncontrolled tumors from controlled tumors with imaging modalities.

Adolescent↗
PubMed2002

MEK/ERK pathway protects ionizing radiation-induced loss of mitochondrial membrane potential and cell death in lymphocytic leukemia cells.

MEK/ERK-mediated signals have recently been found to inhibit Fas-mediated cell death through inhibition of caspase-8 activity. It remains unknown whether MEK/ERK-mediated signals affect ionizing radiation (IR)-induced cell death. Here we demonstrate that MEK/ERK-mediated signals selectively inhibit IR-induced loss of mitochondrial membrane potential (DeltaPsi(m)) and subsequent cell death. In Jurkat cells, TPA strongly activated ERK and inhibited the IR-induced caspase-8/Bid cleavage and the loss of DeltaPsi(m). The inhibitory effect of TPA was mostly abrogated by pretreatment of a specific MEK inhibitor PD98059, indicating that the effect depends upon MEK/ERK-mediated signals. Moreover, BAF-B03 transfectants expressing IL-2 receptor (IL-2R) beta(c) chain lacking the acidic region, which is responsible for MEK/ERK-mediated signals, revealed higher sensitivity to IR than the transfectants expressing wild-type IL-2R. Interestingly, the signals could neither protect the DeltaPsi(m) loss nor cell death in UV-irradiated cells. These data imply that the anti-apoptotic effect of MEK/ERK-mediated signals appears to selectively inhibit the IR-induced cell death through protection of the DeltaPsi(m) loss. Our data enlighten an anti-apoptotic function of MEK/ERK pathway against IR-induced apoptosis, thereby implying its contribution to radioresistance.

BH3 Interacting Domain Death Agonist Protein↗
PubMed2002

The proapoptotic BH3-only protein BAD transduces cell death signals independently of its interaction with Bcl-2.

The BH3-only protein BAD binds to Bcl-2 family proteins through its BH3 domain. Recent studies suggest that BAD binds to both Bcl-2 and Bcl-X(L), however mediates its pro-apoptotic functions through inhibition of Bcl-X(L), but not Bcl-2. In this paper we addressed this issue using a BAD mutant within the BH3 domain, by substitution of Asp 119 with Gly (BAD(D119G)), which selectively abrogates an ability to interact with Bcl-2. Confocal microscopy revealed that mutation of BAD at D119 does not affect BAD targeting to the mitochondrial membrane in serum-starved COS-7 cells. However, co-precipitation assays indicated that, whereas wild-type BAD (BADwt) directly interacts with Bcl-2 and Bcl-X(L), BAD(D119G) interacts only with Bcl-X(L). Nevertheless both BADwt and BAD(D119G) could introduce apoptosis and diminish the anti-apoptotic effect of Bcl-2 and Bcl-X(L) in a similar manner in a co-transfection assay. These data thus suggest that Asp119 is a crucial site within the BH3 domain of BAD for interaction of BAD with Bcl-2, but is dispensable for the interaction of BAD with Bcl-X(L), for its targeting to mitochondria, and most importantly, for its pro-apoptotic functions. Thus, we confirm that neutralization of Bcl-2 function is marginal for BAD-mediated apoptosis.

Amino Acid Substitution↗
PubMed2002

Suplatast tosilate inhibits thymus- and activation-regulated chemokine production by antigen-specific human Th2 cells.

BACKGROUND: Suplatast tosilate is an anti-allergic agent that suppresses cytokine production by human Th2 cells. OBJECTIVE: We investigated the effects of suplatast tosilate on the production of thymus- and activation-regulated chemokine (TARC) by T cells from allergic patients with asthma. METHODS: Purified protein derivative (PPD)-specific Th1 cell lines and Dermatophagoides farinae (Der f)-specific Th2 cell lines were established from nine patients with house dust mite-allergic asthma. The effects of suplatast tosilate on mRNA expression of TARC and protein production of TARC from antigen-specific Th1 or Th2 cell lines were investigated after stimulation with relevant antigens or phytohemagglutinin (PHA). In addition, the effects of IL-4, IL-10, and IFN-gamma on TARC production by Der f-specific Th2 cell lines in the presence or absence of suplatast tosilate were studied. RESULTS: Although PPD-specific Th1 cell lines did not produce TARC after stimulation with PPD antigen or PHA, stimulation of Der f-specific Th2 cell lines with Der f antigen or PHA increased production of TARC. Suplatast tosilate significantly and dose-dependently inhibited production of TARC by Der f-specific Th2 cell lines stimulated with either Der f antigen (76.5% inhibition at 100 microg/mL, P < 0.01) or PHA (81.9% inhibition at 100 microg/mL, P < 0.01). TARC production by Der f-specific Th2 cell lines was significantly increased only by activation with IL-4 but not with IL-10 or IFN-gamma; this increase in TARC production was significantly inhibited by suplatast tosilate (97.5% inhibition at 100 microg/mL, P < 0.01). CONCLUSION: Suplatast tosilate inhibits TARC production by human Th2 cells. Therefore, this agent inhibits both Th2 cytokine and Th2 chemokine and may be a useful anti-allergic agent.

Adult↗
PubMed2002

Transmural pressure induces IL-6 secretion by intestinal epithelial cells.

Although intestinal epithelial cells (IECs) are known as an important source for IL-6, it is not known whether mechanical forces affect IL-6 production. We investigated how transmural pressure modulates IL-6 synthesis and activation of transcription factors in IECs. Pressure was loaded onto IEC-18 cells by introducing compressed helium gas into the cell culture flask for 1-48 h. IL-6 release into the culture media was determined by cell proliferation bioassay using an IL-6-dependent mouse hybridoma cell line (7TD1). Exposure to pressure (80 mmHg) significantly enhanced IL-6 release into the culture media from IEC-18 cells at 12 h. Under control conditions, IL-6 secretion was directed to the basolateral side, but after exposure to pressure IL-6 secretion was increased in both the apical and basolateral sides. A nuclear factor kappa B (NF-kappaB) decoy reversed completely the pressure-induced increase of IL-6 secretion by IEC-18 cells. Pressure treatment enhanced IL-6 mRNA expression in IECs within 6 h. Pressure loading significantly enhanced the activation of both NF-kappaB and NF-IL-6 from 1h in the nuclear protein of IEC-18 cells as assessed by the electrophoretic mobility shift assay using FITC-conjugated specific primers. Increased phosphorylation of I-kappa B was also demonstrated in the cytosol of IEC cells within 1h by Western blot analysis. These results suggest a possible role for pressure loading in immune modulation of the intestinal mucosa by the stimulation of IL-6 release from intestinal epithelial cells.

Animals↗
PubMed2002

Analysis of gene expression during maturation of immature dendritic cells derived from peripheral blood monocytes.

Dendritic cells (DCs) are the most important antigen-presenting cells. Many recent studies have compared the function of immature DCs (iDCs) and mature DCs (mDCs), but there have been few reports of the molecular changes that occur in DCs during maturation. Here, we report on differential gene expression in iDCs generated from peripheral blood monocytes compared with mDCs. Gene expression was evaluated using the differential display method after activation of iDCs with a low concentration of lipopolysaccharide (LPS) to induce maturation. Proteasome subunit alpha type 3 (PSMA3), transcription factor EC (TFEC) isoform and BTK region clone 2f10-rpi were transiently upregulated. Tryptophanyl-tRNA synthetase and CD63 antigen were upregulated for at least 24 h. Neuronal apoptosis inhibitory protein (NAIP) and transforming growth factor-beta-induced 68 kDa protein were downregulated. This is the first report of NAIP expression in human DCs. By comparing the expression of NAIP with that of other members of the inhibitor of apoptosis protein (IAP) family and the Bcl-2 family, only NAIP was found to be strongly expressed in iDCs before stimulation by LPS. PSMA3 was also induced in the DCs stimulated with immune complex. These findings might contribute to our understanding of DC maturation and the effectiveness of DC-based vaccines.

Apoptosis↗
PubMed2002

Hypothalamo-pituitary hypothyroidism detected by neonatal screening for congenital hypothyroidism using measurement of thyroid-stimulating hormone and thyroxine.

UNLABELLED: The optimal strategy in neonatal screening for congenital hypothyroidism is still a subject of controversy. In Kanagawa Prefecture in Japan, simultaneous thyroid-stimulating hormone (TSH) and T4/fT4 determination has been used, while the results of our program may provide valuable information. Cumulative findings were analysed to determine the type and frequency of thyroid disorders in infants detected by simultaneous TSH and T4/fT4 determination, and the TSH and T4/fT4 screening strategy was validated. A total of 1284130 neonates were screened between October 1979 and September 1997 and infants followed because of low T4/fT4 without elevated TSH (T4 < 51.5 nmol/L or fT4 < 9 pmol/L and TSH < 15 mU/L) were retrospectively analysed. The first survey was carried out within 6 mo of birth and the second in 1998; 258 infants were diagnosed with congenital hypothyroidism at the first medical evaluation, 15 of them with hypothalamo-pituitary hypothyroidism. However, in the second survey, only 8 children were confirmed as having hypothalamo-pituitary hypothyroidism, therefore the incidence detected by the present strategy was 1/160516. Of 8 children with hypothalamo-pituitary hypothyroidism, mental retardation was prevented in 3 owing to early treatment. CONCLUSIONS: Simultaneous measurement of TSH and T4/fT4 is a useful strategy for detecting hypothalamo-pituitary hypothyroidism, but more studies are needed to show the cost-benefits of using this strategy.

Congenital Hypothyroidism↗
PubMed2002

Effect of air pollution and environmental tobacco smoke on serum hyaluronate concentrations in school children.

OBJECTIVES: To evaluate serum hyaluronate concentrations relative to air pollution, environmental tobacco smoke (ETS), and respiratory health in Japanese school children. METHODS: Respiratory symptoms and serum IgE concentrations were examined in 1037 school children living in four communities in Japan with differing levels of air pollution. Serum hyaluronate concentrations were assayed in 230 children, consisting of all the children who had symptoms of either asthma or wheeze (65 and 50 subjects, respectively) and normal controls adjusted for sex, school grade, and school without these symptoms (115 subjects). RESULTS: Although serum hyaluronate concentrations did not differ for either asthma or wheeze, the concentrations were significantly higher in children living in communities with higher levels of air pollution. Children with asthma or wheeze and those with serum IgE concentrations of 250 IU/ml or above showed differences in hyaluronate concentrations that related to the degree of air pollution in the communities. In children with higher serum IgE concentrations, the hyaluronate concentrations among subjects exposed to ETS were significantly higher than among those without exposure to ETS. CONCLUSIONS: The present results suggest that serum hyaluronate concentration is related to the degree of air pollution and exposure to ETS. Children with asthma or wheeze and children with higher IgE concentrations are considered to be more susceptible to environmental factors.

Air Pollution↗
PubMed2002

Correlation between the bronchial subepithelial layer and whole airway wall thickness in patients with asthma.

BACKGROUND: The epithelial reticular basement membrane (Rbm) of the airway wall thickens in patients with asthma. However, whether the thickening parallels whole airway wall thickening, which limits airflow, is unknown. The aim of this study was to examine the correlation between the bronchial Rbm thickening and whole airway wall thickening in asthma. In addition, the association of Rbm and whole wall thickening with airflow obstruction was examined. METHODS: Forty nine patients with asthma and 18 healthy control subjects took part in the study. The Rbm thickness was measured in bronchial biopsy specimens and whole airway wall thickness was assessed with high resolution computed tomographic (HRCT) scanning after pretreatment with oral steroids for 2 weeks and inhaled beta2 agonist to minimise reversible changes of the airway walls. The percentage airway wall area (WA%; defined as (wall area/total airway area) x 100) and percentage airway wall thickness (WT%; defined as [(ideal outer diameter - ideal luminal diameter)/ideal outer diameter] x 100) were determined from HRCT scans to assess whole airway wall thickness. Spirometric tests were also performed. RESULTS: WA% and WT% were higher in patients with asthma than in healthy subjects. Both WA% and WT% were strongly correlated with Rbm thickness. Moreover, these three indices of airway wall thickness were inversely correlated with the percentage of predicted forced expiratory volume in 1 second in patients with asthma. CONCLUSIONS: These findings indicate that Rbm thickening parallels whole airway wall thickening which can cause irreversible airflow obstruction in patients with asthma.

Asthma↗
PubMed2002

Role of MRP4 and MRP5 in biology and chemotherapy.

Nucleotide efflux (especially cyclic nucleotides) from a variety of mammalian tissues, bacteria, and lower eukaryotes has been studied for several decades. However, the molecular identity of these nucleotide efflux transporters remained elusive, despite extensive knowledge of their kinetic properties and inhibitor profiles. Identification of the subfamily of adenosine triphosphate (ATP) binding cassette transporters, multidrug resistance protein (MRP) subfamily, permitted rapid advances because some recently identified MRP family members transport modified nucleotide analogs (ie, chemotherapeutic agents). We first identified, MRP4, based on its ability to efflux antiretroviral compounds, such as azidothymidine monophosphate (AZT-MP) and 9-(2-phosphonyl methoxyethyl) adenine (PMEA), in drug-resistant and also in transfected cell lines. MRP5, a close structural homologue of MRP4 also transported PMEA. MRP4 and MRP5 confer resistance to cytotoxic thiopurine nucleotides, and we demonstrate MRP4 expression varies among acute lymphoblastic leukemias, suggesting this as a factor in response to chemotherapy with these agents. The ability of MRP4 and MRP5 to transport 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP) suggests they may play a biological role in cellular signaling by these nucleotides. Finally, we propose that MRP4 may also play a role in hepatic bile acid homeostasis because loss of the main bile acid efflux transporter, sister of P-glycoprotein (SPGP) aka bile-salt export pump (BSEP), leads to a strong compensatory upregulation in MRP4 expression. Cumulatively, these studies reveal that the ATP-binding cassette (ABC) transporters MRP4 and MRP5 have a unique role in biology and in chemotherapeutic response.

Animals↗
PubMed2002

Nuclear export of glucocorticoid receptor is enhanced by c-Jun N-terminal kinase-mediated phosphorylation.

The c-Jun N-terminal kinase (JNK) phosphorylates the glucocorticoid receptor (GR) and inhibits GR-mediated transcription. However, the biological effect of the GR phosphorylation remains unknown. Here we demonstrate that activated JNK phosphorylates human GR at Ser226 and enhances its nuclear export after withdrawal of a ligand for GR, dexamethasone. At 1 h after dexamethasone withdrawal, green fluorescent protein-GR molecules were mostly retained at the nucleus, whereas UV exposure enhanced its nuclear export, and approximately 30-40% of cells revealed distinct nuclear export. JNK overexpression alone mimics UV exposure and enhanced GR export accompanied by inhibition of GR-mediated transcription. However, mutation of the Ser226 JNK phosphorylation site in GR abrogated UV-mediated enhancement of GR nuclear export. Furthermore, overexpression of a dominant negative SEK1 mutant also abrogated the effects of UV exposure on GR export. Taken together, these findings suggest that JNK-mediated phosphorylation of the GR-Ser226 enhances GR nuclear export and may contribute to termination of GR-mediated transcription.

Active Transport, Cell Nucleus↗
PubMed2001

Adenovirus-mediated transfection of caspase-8 augments anoikis and inhibits peritoneal dissemination of human gastric carcinoma cells.

Caspase-8 is a member of the cysteine protease family that modulates apoptosis induced by a variety of cell death signals and has recently been found to be activated during the process of anoikis, which is a form of apoptosis caused by loss of anchorage in epithelial cells. We previously demonstrated that the inhibition of anoikis promotes peritoneal dissemination of human gastric carcinoma MKN45 cells, which are anchorage dependent. This suggests that augmentation of anoikis may suppress dissemination of carcinoma cells. To determine whether extrinsic overexpression of caspase-8 can augment anoikis in MKN45 cells, we transfected them with the caspase-8 gene using an adenoviral (Adv) vector (Adv-caspase-8). Here we demonstrate that Adv-caspase-8 infection, at 15 multiplicity of infection (MOI), can augment anoikis in MKN45 cells and suppresses MKN45 peritoneal dissemination in SCID mice. The inhibitory effect on peritoneal dissemination resulted in a prolonged survival compared with that in control mice. In contrast, the Adv-caspase-8 (15 MOI) had no distinct effect on cell viability or growth either of attached MKN45 cells or of s.c. tumor growth in SCID mice. Thus, Adv-mediated overexpression of caspase-8 suppressed peritoneal dissemination mainly through augmentation of anoikis. In addition, Adv-caspase-8-mediated augmentation of anoikis was similarly observed in another gastric carcinoma MKN74 cell line. In contrast, Adv-p53 could not augment anoikis in MKN45 cells. These results imply that Adv-mediated gene transfer of caspase-8 can selectively induce apoptosis in detached carcinoma cells and, thus, shows potential as a novel cancer therapy against dissemination of gastric and probably other carcinoma cells originating from epithelial tissues.

Adenocarcinoma↗