Treatment outcome of definitive endoesophageal brachytherapy for epithelial or intramucosal esophageal cancer.
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Aged↗
Biomedical subjects
Y Akagi
Publications and source records attributed to Y Akagi.
Regulation of vascular endothelial growth factor expression in human colon cancer by insulin-like growth factor-I.
We investigated the role of insulin-like growth factor (IGF)-I and IGF-binding proteins (IGFBPs) in the regulation of vascular endothelial growth factor (VEGF) expression in colon cancer cells and the mechanism by which this regulation occurs. HT29 human colon cancer cells were treated with IGF-I for various time periods. VEGF mRNA expression increased within 2 h and peaked at 24 h. SW620 colon cancer cells exhibited a peak induction of VEGF mRNA 8 h after IGF-I treatment. IGF-I induction of VEGF was confirmed at the protein level. In experiments using transient transfection of VEGF promoter-reporter constructs into HT29 cells, IGF-I increased the activity of the VEGF promoter, and pretreatment of HT29 cells with dactinomycin abrogated the induction of VEGF mRNA by IGF-I. The half-life of VEGF mRNA was not prolonged by treatment with IGF-I. Blocking the activity of IGFBP-4 did not significantly modulate the effect of IGF-I induction of VEGF mRNA in HT29 cells. Treating cells with des-(1-3)-IGF-I (an active derivative of IGF-I that does not bind to binding proteins) had effects on VEGF mRNA expression that were similar to those of IGF-I. These findings suggest that IGF-I regulates VEGF expression in human colon cancer cells by induction of transcription of the VEGF gene. IGFBPs do not significantly affect IGF-I induction of VEGF.
Colonic Neoplasms↗
Treatment results of stage I and II oral tongue cancer with interstitial brachytherapy: maximum tumor thickness is prognostic of nodal metastasis.
PURPOSE: To evaluate the prognostic importance of T classification and maximum tumor thickness (MTT) on the treatment results of Stage I and II oral tongue cancer treated with interstitial brachytherapy. METHODS AND MATERIALS: Between January 1981 and December 1993, 173 cases were eligible for this retrospective analysis. Of 173 patients, 75 were classified as Stage I and 98 as Stage II: maximum tumor length ranged from 6 to 40 mm. MTT, which ranged from 2 to 38 mm, was measured with ultrasonography and/or palpation. Brachytherapy was performed with iridium hairpins or radium needles following external irradiation in 66 patients, or exclusively in 107 patients. RESULTS: The 5-year local recurrence rates were Stage I, 7%; Stage II, 22%; MTT < 8 mm, 8%; and MTT > or = 8 mm, 28%. The 5-year regional recurrence rates were Stage I, 15%; Stage II, 29%; MTT < 8 mm, 18%; and MTT > or = 8 mm, 31%, respectively. The 5-year local recurrence rates of the patients with Stage I and MTT < 8 mm of the brachytherapy only group were significantly better than those of Stage II and MTT > or = 8 mm (5% and 6% vs. 16% and 24%). The 5-year regional recurrence rates of the patients with Stage I and MTT < 8 mm of the brachytherapy-only group were significantly better than those of Stage II and MTT > or = 8 mm (14% and 16% vs. 34% and 46%). There was no significant difference in the 5-year regional recurrence rates between the two groups of Stage I and Stage II, MTT < 8 mm. However, there was a significant difference in the 5-year regional recurrence rates between the two groups of MTT > or = 8 mm (p < 0.005). CONCLUSIONS: For patients with Stage I and II oral tongue cancer, tumor thickness as well as T classification were prognostic for nodal metastasis and prognosis. Patients with MTT > or = 8 mm are more likely to fail in the neck region. These findings suggest that MTT should be considered along with T stage in determining strategies for Stage I and II oral tongue cancer.
Adult↗
Retinal vessel changes in galactose-fed dogs.
BACKGROUND: Retinal lesions similar to those in human early-stage diabetic retinopathy have been reported to occur in dogs fed galactose for long periods. Investigations of retinal changes, however, have been limited to studies of the intact retinal vasculature isolated by trypsin digestion. OBJECTIVE: To document the onset and progression of retinal lesions in galactose-fed dogs by the common clinical techniques of fundus color photography and fluorescein angiography. METHODS: Fourteen 6-month-old male beagles made aphakic in 1 eye were divided into a control group (4 dogs), receiving a diet containing 30% cellulose, and a galactosemic group (10 dogs), receiving a diet containing 30% galactose. The progression of retinal changes in these dogs was periodically monitored by color fundus photography and fluorescein angiography. RESULTS: Dogs fed a 30% galactose diet for 28 to 41 months were observed by fluorescein angiography and color fundus photography to develop, in order of frequency, microaneurysms, retinal hemorrhages, intraretinal microvascular abnormalities, retinal nonperfused areas, and varicose and serpiginous veins. These findings are similar to the early clinical retinal changes observed in humans with diabetes. CONCLUSION: These results confirm that galactosemic dogs are an appropriate and suitable animal model for investigating human diabetic retinopathy.
Animals↗
Surgical treatment of lower rectal cancer with sphincter preservation using handsewn coloanal anastomosis.
The present study was designed to evaluate the technical feasibility and oncologic results of performing handsewn coloanal anastomosis (CAA). A total of 46 patients treated for lower rectal cancer using CAA were retrospectively studied, and the oncologic results were compared with those of 105 patients treated with abdominoperineal resection (APR). CAA was performed in patients who had both good mobility of the tumor and a distal clearance margin of more than 1.0 cm. No significant difference was noted in the mortality rates following the two operations (CAA 2.2% vs APR 1.9%). Pelvic recurrence was detected in two patients (4.5%) after CAA and in six patients (7.2%) after APR. The 5-year survival rate after CAA was 79.2% and that after APR was 72.6%. No significant difference was noted in the incidence of pelvic recurrence or the survival rates between the two operations. These results show that CAA could be an excellent reconstructive option in the treatment of lower rectal carcinoma for selected patients.
Adenocarcinoma↗
Effect of aldose reductase inhibitor on corneal epithelial barrier function in galactose-fed dogs.
The effect of concomitant administration of galactose and the aldose reductase inhibitor(ARI) Epalrestat (Kinedak) on corneal barrier function was examined in dogs. Six-month-old male beagles were rendered aphakic in one eye and then divided into four groups as follows: 1) a control group fed on 30% cellulose, 2) a galactosemic group fed on 30% galactose, 3) a 30% galactose-fed group treated with low dose (20 mg/kg) ARI and 4) a 30% galactose-fed group treated with high dose (50 mg/kg) ARI. Forty-one months after the start of these diets, corneal autofluorescence and the corneal barrier function were measured in each dog using anterior fluorophotometry (FL-500). When barrier function was analyzed in non-operated eyes, fluorescence data were significantly higher in the galactosemic group compared to the control group. In non-operated eyes, fluorescent data in high-dose ARI treated group were significantly lower than those in the galactosemic group. However, in operated eyes, no significant difference was observed between the galactosemic group and the ARI treated groups. Similar trends were observed when corneal autofluorescence of each group was compared. Long-term galactose feeding appeared to damage corneal epithelial barrier function. This damage was not observed in the high-dose ARI treated group suggesting that this damage may be linked to the polyol pathway.
Aldehyde Reductase↗
Enhanced glomerular expression of caldesmon in IgA nephropathy and its suppression by glucocorticoid-heparin therapy.
BACKGROUND: Activation and consequent phenotypic modulation of mesangial cells is considered to play a crucial role in the process of glomerular disease progression. Caldesmon, a calmodulin and actin-binding protein, is a molecular marker of the phenotypic change in smooth-muscle cells. SUBJECTS AND METHODS: We studied whether the expression of caldesmon in mesangial cells was enhanced in the process of IgA nephropathy and whether it would be a marker of mesangial activation indicating prognostic significance in specific disease states. We performed immunohistochemical staining with anticaldesmon and alpha-smooth-muscle actin (alpha-SMA) antibodies in 32 biopsy specimens from IgA nephropathy patients and analysed them quantitatively with a computer-aided manipulator. RESULTS: The glomerular expression of caldesmon was enhanced in IgA nephropathy patients. We compared caldesmon expression with composite histological scores (cell score and matrix score), clinical parameters and expressions of alpha-SMA. There was a statistically significant correlation between the caldesmon score and the histological scores (cell score and matrix score, P<0.0001, P<0.01 respectively). Patients showing a high intensity of caldesmon expression (defined as caldesmon score > or = 35; H-group) had significantly higher urinary protein excretion than those showing a low intensity of caldesmon expression (defined as caldesmon score < 35; L-group) (1.2 +/- 1.2 g/24 h vs 0.41 +/- 0.53 g/24 h, P<0.05). Caldesmon and alpha-SMA expression had a statistically significant correlation (P<0.000). Next, 13 patients were treated with glucocorticoid-heparin for 4-8 weeks and re-biopsies were performed. After the therapy, the caldesmon and alpha-SMA scores were significantly lower than those before the therapy (P<0.01). DISCUSSION: These results suggest that the expression of caldesmon in glomeruli is associated with the progression of IgA nephropathy, and that glucocorticoid heparin therapy may reverse the phenotype of mesangial cells during the disease process of glomerulonephritis.
Actins↗
Metastatic model of human colon cancer constructed using orthotopic implantation in nude mice.
Nude mice have been used to grow subcutis (s.c.) growing human colorectal tumors, but these tumors rarely metastasize. This is a problem for studies into the biological behavior of metastatic subpopulations of human colorectal cancers. We have followed the evolution of the parental line and of a variant of human colon carcinoma KM12 cells, that were both tumorigenic, following implantation into the s.c. or cecal wall of nude mice. The tumors growing s.c. did not produce visceral metastases, whereas the cecal tumors metastasized to the regional mesenteric lymph nodes and to the liver. However, the incidence of liver metastases was different between the parental cell line KM12C cells and the in vivo selected cell line KM12SM cells after orthotopic inoculation. The morphological findings of KM12 cells proliferating in a monolayered sheet revealed that these two cell lines consisted of various cell populations. These results suggest that in the orthotopic colon cancer models, liver metastasis is defined by difference in subpopulations of metastatic phenotypes to the liver with early dominance of its growth in the implanted organ. As a result, our new model using orthotopic implantation of KM12SM cells, which produce a 50% incidence of liver metastasis, can help to provide a technique to study the biological behavior of metastatic subpopulations of human colon cancers.
Animals↗
[Role of adhesion molecules in tonsillar focal infection].
Pustulosis palmaris et plantaris (PPP) is a pustular skin disease that is closely related to tonsillar focal infection. Patients with this skin disease have shown marked improvements of skin lesions after tonsillectomy. In this study, we evaluated the role of adhesion molecules in the pathogenesis of tonsillarfocal infection related to PPP. The results were that tonsillar lymphocytes of patients with PPP adhered to vessels in the dermis, to vessels running through the dermal papilla, and to vessels in the epidermis at the base of pustules. The adhesion of tonsillar lymphocytes to endothelial cells were significantly blocked by anti-LFA-1 antibody. An immunohistological study revealed that cells infiltrating the dermis expressed LFA-1, whereas ICAM-1, the ligand of LFA-1, was detected on endothelial cells and keratinocytes. It is interesting to note that cells infiltrating the dermis of the erythema stage or the pustule stage of PPP expressed ICAM-1, and the vessels in these stages expressed E-selectin. ICAM-1 was also detected on vessels in the dermis of skin that seemed to be macroscopically normal. These results suggest that tonsillar lymphocytes may have an affinity for the skin of PPP-expressing adhesion molecules such as LFA-1, ICAM-1, and E-selectin. These adhesion molecules seem to be easily activated, not only in skin lesions of PPP, but also in macroscopically normal areas resulting in cellular infiltration and pustule formation.
Adult↗
[Quality of life assessment in radiation therapy].
Cancer treatment outcome should be evaluated not only with conventional parameters of survival, local control, and response rate, but with quality-of-life (QOL) based parameters. As radiation therapy is a treatment to eradicate cancer without resection of tissues or organs, a better functional or cosmetic result could be obtained compared with surgical treatment. If basically functional or cosmetic results are better, QOL of the patient could be expected to be even more superior. Patient QOL should be assessed from the physical, psychological, and social standpoints. So, adequate instruments or scoring systems are essential to obtain data. In this paper, we introduce an outline of QOL-related research activities in cancer treatment, especially in radiation therapy. We also attempt to assess the functional outcome and late complications, which would affect patient QOL. Finally, the concept of quality adjusted survival time or utility analysis is also mentioned.
Esophageal Neoplasms↗
Significance of platelet-derived endothelial cell growth factor in the angiogenesis of human gastric cancer.
We have previously shown that platelet-derived endothelial cell growth factor (PD-ECGF) is associated with angiogenesis of human colon cancer; this factor is expressed at high levels in vascular tumors that express low levels of vascular endothelial growth factor (VEGF). In these colon cancers, the major source of PD-ECGF is the infiltrating cells. In this study, we examined the role of PD-ECGF in the angiogenesis of human gastric cancer. Immunostaining for PD-ECGF was done on 93 gastric cancers previously stained for VEGF, basic fibroblast growth factor, and factor VIII-related antigen (specific for endothelial cells). To determine the cell type expressing PD-ECGF, double staining was done using antibodies to both PD-ECGF and CD68 (specific for macrophages). PD-ECGF was expressed more frequently in infiltrating cells (positive CD68 staining; 53.8%) than in tumor epithelium (9.7%; P < 0.0001). Infiltrating cells simultaneously stained positive for both PD-ECGF and CD68. An association between PD-ECGF expression in infiltrating cells, VEGF expression in tumor epithelium, and vessel count was observed in intestinal-type gastric cancer but not in diffuse-type gastric cancer. Vessel count was greater in tumors with high expression of both PD-ECGF and VEGF than in those with high expression of either factor alone (P = 0.002). Multiple angiogenic factors expressed by both tumor cells and infiltrating cells may play a role in the regulation of angiogenesis in intestinal-type gastric cancer.
Adult↗
Cholecystokinin stimulates ascorbic acid secretion through its specific receptor in the perfused stomach of rats.
We have previously demonstrated that endogenous ascorbic acid is secreted into the gastric lumen by cholinergic stimulation in both conscious pylorus-ligated rats and the perfused stomach of unconscious rats, and that gastrin, a potent gastric stimulatory peptide hormone, has no effect. In the present study, the effects of some gastrointestinal peptide hormones on gastric ascorbic acid secretion were further examined in the perfused stomach of rats. An intravenous administration of cholecystokinin octapeptide (CCK-8) significantly increased gastric ascorbic acid secretion at a dose of 1.0 and 4.0 micrograms/kg, whereas the other three peptides examined, bombesin, neurotensin and substance P, showed no or little effect at the doses which were quite commonly employed for evaluation of various gastric functions. CCK-8-induced ascorbic acid secretion was reduced by pretreatment with proglumide, which is a CCK receptor antagonist, but not by pretreatment with atropine. These results indicate that gastric ascorbic acid secretion is physiologically regulated not only by muscarinic receptor-associated cholinergic stimulation but also by CCK receptor-associated humoral stimulation.
Animals↗
3-FG as substrate for investigating flux through the polyol pathway in dog lens by 19F-NMR spectroscopy.
PURPOSE: To investigate flux through the polyol pathway in the dog lens by 19F-nuclear magnetic resonance (19F-NMR) spectroscopy, using 3-fluoro-3-deoxy-D-glucose (3-FG) as a substrate. METHODS: 3-FG metabolism was monitored by 19F-NMR analysis. Dog lenses were incubated in Dulbecco's modified Eagle's medium containing 10 mM 3-FG. Enzymatic reductase and dehydrogenase activities were spectrophotometrically determined, whereas the analyses of 3-FG metabolites were conducted by 19F-NMR analysis. Aldose reductase (AR) was immunohistochemically localized in dog lens with antibodies raised against dog kidney AR. RESULTS: 19F-NMR spectra indicate that incubation of purified dog lenses AR with 3-FG results in the formation of 3-fluoro-3-deoxy-D-sorbitol (3-FS) and that incubation of dog liver sorbitol dehydrogenase (SDH) with 3-FS results in the formation of 3-fluoro-3-deoxy-D-fructose (3-FF). This confirms that 3-FG is metabolized to 3-FF by the polyol pathway enzymes. The affinity (Km) of AR for 3-FG is approximately 20-fold better than that for D-glucose, whereas the Km of SDH for 3-FS was fourfold less than for D-sorbitol. 3-FG in cultured dog lenses is metabolized primarily to 3-FS; however, small amounts of 3-FF and 3-fluoro-3-deoxy-D-gluconic acid (3-FGA) are also formed. 3-FS formation was reduced by the AR inhibitor AL 1576, and 3-FF formation was eliminated by the SDH inhibitor CP-166,572. In dog lens epithelial cells cultured with 3-FG, only 3-FS is formed. Similarly, only 3-FS is formed when lens capsule containing primarily epithelial lens contaminated with superficial epithelial cells was incubated in 3-FG. Similar incubation of the remaining cortex resulted primarily in the formation of 3-FS and 3-FGA. This enzymatic distribution was confirmed by spectrophotometric activity analysis and the immunohistochemical localization of AR. CONCLUSIONS: The data confirm that flux through the polyol pathway primarily results in sorbitol accumulation. The absence of fructose and gluconic acid from cultured lens epithelium suggests that the epithelial cells primarily contain AR, whereas differentiated fiber cells also contain SDH and glucose dehydrogenase.
Aldehyde Reductase↗
Towards gene therapy for renal diseases.
The rationale of the somatic gene therapy is the correction of diseases at the most fundamental level. Ideal gene therapy should be achieved by the replacement of the wrong gene sequence of genome with correct one. However, the gene technology to date is yet immature so as to correct the wrong gene sequence in vivo. Potentially, the present technology of gene transfer may provide: 1) correction of cellular dysfunction by expressing the deficient gene; 2) addition of new function for a cell by transferring an exogenous gene; 3) inhibition of unfavorable action of a cell by introducing a counteracting gene. In nephrology, the gene transfer targeted kidney has been challenged at the experimental level. HVJ-liposome method and recombinant adenovirus allow gene transfer to the particular cells in kidney in vivo. Ex vivo gene transfer using mesangial cells and macrophages are another option. Transplant kidney is also a good material for genetic engineering. The potential application of gene transfer is enormous while the therapeutic application have just begun to explored. We have been devoted to HVJ-liposome mediated gene transfer to the kidney and successfully demonstrated the suppression of the extracellular matrix accumulation of the glomeruli in the experimental glomerulonephritis through inhibition of the TGF-beta action by antisense oligonucleotides or soluble type receptor chimera for TGF-beta. We also applied this technology to the inhibition of interstitial fibrosis in unilateral ureter obstruction model. The new HVJ-liposome method improved in lipid composition allows gene transfer to tubulointerstitial fibroblast by retrograde approach from ureter. In consequence, introduced TGF-beta antisense suppressed the TGF-beta mRNA in concomitant with ameliorating interstitial fibrosis. We believe that the gene transfer technique will become common strategy to study the molecular aspect of the renal diseases and will be possibly applicable to molecular intervention in nephrology.
Animals↗
Cloning, functional expression and tissue distribution of rabbit alpha1a-adrenoceptor.
A cDNA clone, which has an open reading frame of 1398 nucleotides encoding a 466-amino-acid peptide, has been isolated from rabbit liver cDNA library. Compared with the peptide sequence, it shows high homology to alpha1a adrenoceptors of human, bovine and rat. We expressed this clone in COS-7 and investigated the pharmacological properties, revealing similarity to those of human alpha1a adrenoceptors. Competitive RT/PCR has detected the mRNA in variety of rabbit tissues, especially abundantly in liver, vas deferens, brain, and aorta, but not in heart.
Amino Acid Sequence↗
Transcriptional activation of a hybrid promoter composed of cytomegalovirus enhancer and beta-actin/beta-globin gene in glomerular epithelial cells in vivo.
The aim of this study was to seek a promoter, transactivated selectively in renal cells in vivo by using transgenic (tg) mouse technology. We generated two kinds of tg mouse lines carrying a green fluorescence protein (GFP) cDNA driven either by cytomegalovirus enhancer and beta-actin/beta-globin promoter (CX-GFP) or by elongation factor 1alpha promoter (EF-GFP), and investigated the expression of GFP in the kidney. Microscopic examination of the renal tissues in CX-GFP-tg mice revealed that GFP was expressed only in glomeruli, mainly epithelial cells, but not in tubules, arteries and interstitium. Moreover, in situ hybridization demonstrated that GFP mRNA expression was localized in the glomerular cells. In contrast, GFP was not detectable in the kidney in any of the lines of EF-GFP-tg mouse. To exclude the possible involvement of the GFP cDNA as an enhancer, we constructed tg mice carrying the CX promoter driving a human CD4 cDNA. It was confirmed that the expression patterns of human CD4 in the kidney were quite similar to those of GFP in the kidney of CX-GFP-tg mice. These results strongly suggest that CX promoter could be transactivated in glomerular epithelial cells in vivo.
Actins↗
Molecular intervention with antisense oligodeoxynucleotides (ODNs) in nephrology.
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Animals↗
Application of gene therapy to diabetic nephropathy.
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Animals↗