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T Nakajima

Publications and source records attributed to T Nakajima.

At least 145 records · Page 8Linked to original sources
PubMed2001

TGF-alpha inhibits apoptosis of murine gastric pit cells through an NF-kappaB-dependent pathway.

BACKGROUND AND AIMS: Recently, some growth factors have been shown to play roles not only as growth factors but also as cell-surviving factors. Transforming growth factor (TGF)-alpha is expressed in normal gastric mucosa. In this study, we investigated the cell-surviving effect of TGF-alpha on gastric mucosal cells and its signaling mechanism. METHODS: We used a gastric mucosal cell line, GSM06, and gastric cancer cell line, AGS. Apoptosis was induced by serum depletion or exposure to sodium butyrate. Analysis of apoptosis was performed by DNA ladder assay, measuring the DNA fragmentation ratio (Burton method), and 4',6-diamidino-2-phenylindole staining. RESULTS: TGF-alpha protected gastric mucosal cells against apoptosis induced by serum depletion or sodium butyrate in a dose-dependent manner. This antiapoptotic effect of TGF-alpha was blocked by the pretreatment with reagents that can potentially inhibit NF-kappaB activation, whereas neither MEK inhibitor PD098059 nor PI-3-kinase inhibitor wortmannin abolished this effect. Electrophoretic mobility shift assay showed nuclear factor kappaB (NF-kappaB) activation by TGF-alpha stimulation. TGF-alpha also enhanced the expression of Bcl-2 family proteins in an NF-kappaB-dependent manner. CONCLUSIONS: TGF-alpha plays an antiapoptotic role in gastric mucosal cells via the NF-kappaB-dependent pathway.

Animals↗
PubMed2001

Analysis of K-ras, APC, and beta-catenin in aberrant crypt foci in sporadic adenoma, cancer, and familial adenomatous polyposis.

BACKGROUND & AIMS: We have previously shown that aberrant crypt foci (ACF) are the putative precursor lesions of colorectal adenomas and subsequent cancer in humans using magnifying endoscopy. The present study was designed to investigate these genetic alterations in ACF biopsy specimens from normal subjects, familial adenomatous polyposis (FAP) or sporadic patients. METHODS: The non-FAP cases included 34 normal subjects, 35 colorectal adenoma patients, and 19 colorectal cancer patients; there were 4 FAP patients. Biopsies were performed on ACF by magnifying endoscopy. K-ras mutations were analyzed by 2-step polymerase chain reaction and restriction fragment length polymorphism, APC mutations by in vitro-synthesized protein assay, and beta-catenin mutations by direct sequencing. Full-length APC and beta-catenin were detected by immunofluorescence. RESULTS: In non-FAP cases, K-ras mutations were detected in 82% (89/106) of nondysplastic ACF and 63% (17/27) of dysplastic ACF. APC mutation and beta-catenin accumulation were not detected in non-FAP ACF, whereas in adenoma of these patients, positivity of APC mutation and beta-catenin accumulation were 78% (24/31), and that of K-ras mutation was 65% (20/31). FAP patients showed K-ras mutations in only 13% (1/8) of dysplastic ACF, which is the predominant form of ACF found in FAP. In FAP patients, somatic APC mutations were found in 100% of dysplastic ACF, as they are in adenoma. The frequency of K-ras mutations was 73% (8 of 11) in FAP adenoma. CONCLUSIONS: The data suggest that in sporadic colorectal carcinogenesis, assuming the biological implication of ACF as a precursor of adenomas, there is a route where K-ras mutation mainly occurs during the formation of ACF, which then become adenomas wherein APC mutation occurs. In FAP, however, somatic mutation of APC predominantly occurs during ACF formation, followed by K-ras mutation.

Adenomatous Polyposis Coli↗
PubMed2001

Glutathione S-transferase-pi overexpression is closely associated with K-ras mutation during human colon carcinogenesis.

BACKGROUND & AIMS: In colorectal adenoma and carcinoma, glutathione S-transferase-pi (GSTP1-1) is highly expressed. K-ras mutation is also known to occur frequently in colorectal adenoma and carcinoma, as well as in the putative precursor of adenoma, aberrant crypt foci (ACF). Further, forced expression of v-H-ras in rat liver epithelial cells has been shown to enhance rat pi-class GST expression. The aim of the present study is, therefore, to investigate the causative relationship between GSTP1-1 overexpression and K-ras mutation in these lesions. METHODS: Twenty-seven specimens of colorectal carcinoma, 24 of adenoma, and 28 of ACF were examined in this study. The expression of GSTP1-1 or p21(K-ras) was examined by immunohistochemistry. The GSTP1-1 messenger RNA levels were measured by TaqMan reverse-transcription polymerase chain reaction (PCR). K-ras mutation was detected by two-step PCR restriction fragment length polymorphism. v-K-ras transfection to RPMI-4788 colon carcinoma cells was carried out by the lipofection method. Activities of GSTP1-1 promoters containing AP-1 and Sp1 responsive elements in the v-K-ras transfectants were measured by a secreted form of human placental alkaline phosphatase (SEAP) assay. Nuclear protein from these transfectants bound to the GSTP1-1 promoter was analyzed by electrophoretic mobility shift assay (EMSA). RESULTS: In human colorectal carcinoma, adenoma, and ACF, close association of increased expression of GSTP1-1 with K-ras mutation was observed. v-K-ras transfectants showed significantly higher SEAP activity than that of mock-transfectant activity. EMSA showed specific interaction of AP-1 with promoter of GSTP1-1. CONCLUSIONS: It is highly plausible that GSTP1-1 overexpression in ACF, colorectal adenoma, and carcinoma is induced by K-ras mutation via AP-1 activation.

Adenoma↗
PubMed2001

Proliferative activity of intrahepatic colorectal metastases after preoperative hemihepatic portal vein embolization.

Although hemihepatic portal vein embolization (PVE) has been used preoperatively to extend indications for hepatectomy in patients with colorectal metastases, the effects of this procedure on tumor growth and outcome remain controversial. To address this issue, we assessed the proliferative activity of intrahepatic metastases after PVE and the long-term outcome of this procedure. Eighteen patients with colorectal metastases underwent preoperative PVE between 1996 and 2000 (PVE group). Twenty-nine patients who underwent major hepatic resection without PVE served as control (non-PVE group). The hepatic parenchymal fraction of the left lobe had significantly increased from 38.1 +/- 3.2% to 45.9 +/- 2.9% 3 weeks after PVE (+20.5%, P <.0001). Tumor volume and percent tumor volume had also significantly increased from 223 +/- 89 mL to 270 +/- 97 mL (+20.8%, P =.016) and from 13.7 + 4.3% to 16.2 + 4.9% (+18.5%, P =.014), respectively. There was no apparent correlation between the increase in parenchymal volume and that in tumor volume. The Ki-67 labeling index of metastatic lesions was 46.6 +/- 7.2% in the PVE group and 35.4 +/- 12.6% in the non-PVE group (P =.013). Long-term survival was similar in the PVE and non-PVE groups, however, disease-free survival was significantly poorer in the PVE group than in the non-PVE group (P =.004). We conclude that PVE increases tumor growth and probably is associated with enhanced recurrence of disease. Although PVE is effective in extending indications for surgery, patient selection for PVE should be cautious.

Adult↗
PubMed2001

The ligands/activators for peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma increase Cu2+,Zn2+-superoxide dismutase and decrease p22phox message expressions in primary endothelial cells.

We examined the effects of a variety of ligands/activators of the peroxisome proliferator-activated receptor (PPAR) on the expression of the superoxide scavenger enzyme, Cu2+,Zn2+-superoxide dismutase (CuZn-SOD), and the superoxide generating enzyme nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) oxidase in primary cultures of human umbilical vein endothelial cells (HUVEC) and human aorta endothelial cells (HAEC). Our data show that 3 types of PPARs, PPARalpha, PPARbeta/delta/Nuc1, and PPARgamma are expressed in endothelial cells. Bezafibrate, which is a ligand/activator for PPARalpha, increased the CuZn-SOD gene expression and protein levels in endothelial cells. Troglitazone and pioglitazone, which are ligands/activators for PPARgamma, also induced PPARalpha gene and protein expression and increased CuZn-SOD gene expression and protein levels in addition to increasing PPARgamma gene and protein expression in endothelial cells. Moreover, with treatment of monounsaturated and polyunsaturated fatty acids (PUFA), the CuZn-SOD mRNA levels were positively correlated with PPARalpha mRNA levels (r = .872, P < .0001) in primary endothelial cells. In addition, the phorbol myristate acetate (PMA)-stimulated or PMA-nonstimulated 22-kd a-subunit (p22phox) mRNA levels and 47-kd a-subunit (p47phox) protein levels in NADPH oxidase were decreased by treatment with PPARalpha and PPARgamma ligands/activators. These results suggest that PPARalpha and PPARgamma gene and protein expression in endothelial cells may play a physiologic role as radical scavengers, although the details of these mechanisms remain to be established.

Cells, Cultured↗
PubMed2001

Changes in masticatory function after orthognathic treatment in patients with mandibular prognathism.

Changes in masticatory function were measured in 27 patients in whom mandibular prognathism was corrected surgically. The mean value of masticatory efficiency before treatment was 46% of that of control subjects with normal occlusion. It improved, but remained at 60% of the control value postoperatively. Similar changes were seen in the number and area of occlusal contacts and the integrated muscle activities of the masseter and temporalis on the chewing side, but the postoperative improvement in masticatory efficiency was mainly the result of improvement in masseter activity. The mean values of masticatory cycle variables in the patient group did not differ significantly from those of the controls. Their preoperative mean coefficients of variation, which were significantly higher than those of the controls, decreased significantly postoperatively. These results suggest that the stability of masticatory rhythm was improved by orthognathic surgery.

Adolescent↗
PubMed2001

Inhibitory effect of baicalein, a flavonoid in Scutellaria Root, on eotaxin production by human dermal fibroblasts.

Eotaxin is an eosinophil-specific chemokine associated with the recruitment of eosinophils to sites of allergic inflammation. "Saiboku-to" (Formula magnoliae et bupleuri) is a kampo herbal medicine used for the treatment of bronchial asthma in Japan. In this study, we investigated the effects of Scutellaria Root, a major herb in Saiboku-to and its components such as baicalein and baicalin on eotaxin production by IL-4 plus TNF-alpha-stimulated human fibroblasts. An extract of Scutellaria Root markedly inhibited eotaxin production. Four major flavonoids from Scutellaria Root were found to show inhibitory activity on eotaxin production at a concentration of 10 micrograms/ml in the order of baicalein > oroxylin A > baicalin > skullcapflavon II. The inhibitory effect of baicalein was expressed in a dose-dependent manner, and almost 50% inhibition was observed at 1.8 micrograms/ml. Furthermore, baicalein prevented human eotaxin mRNA expression in IL-4 plus TNF-alpha-stimulated human fibroblasts. These results help explain the pharmacological efficacy of Scutellaria Root in the treatment of bronchial asthma since it would suppress eotaxin associated recruitment of eosinophils.

Asthma↗
PubMed2001

Failure of exclusion of internal iliac artery aneurysms.

PURPOSE: We investigated in detail the state of internal iliac artery (IIA) aneurysms over the midterm after the exclusion procedure. METHODS: From January 1990 to December 1998, 29 patients underwent the exclusion procedure for IIA aneurysms. The medical records of 27 survivors were retrospectively reviewed, and 30 excluded aneurysms of these patients were followed up with computed tomography scanning over the midterm. RESULTS: In the immediate postoperative period, 26 aneurysms were completely thrombosed, and four were incompletely thrombosed. In the midterm, 24 aneurysms were completely thrombosed (complete group), and six were incompletely thrombosed (incomplete group). No aneurysms expanded or ruptured during the follow-up period from 6 to 98 months (mean, 26 months). The size of the excluded aneurysm decreased in 22 of 24 aneurysms in the complete group, but no change in size was noted in the six aneurysms in the incomplete group. The preoperative size of the IIA aneurysm in the incomplete group was significantly larger than that in the complete group (P =.0047). The size of two aneurysms in the incomplete group was smaller than 3.0 cm. The aneurysms in the incomplete group extended significantly deep into the pelvis as compared with those in the complete group (P =.0008). CONCLUSIONS: The exclusion of IIA aneurysm did not reliably result in thrombosis of the aneurysm. For IIA aneurysms extending deeply into the pelvis, even if the size of the aneurysm is smaller than 3.0 cm, the exclusion procedure should not be performed.

Aged↗
PubMed2001

Effects of the inhalation of diesel exhaust, Kanto loam dust, or diesel exhaust without particles on immune responses in mice exposed to Japanese cedar (Cryptomeria japonica) pollen.

To assess the potential enhancement by air-pollutants of immune responses in mice, especially with regard to allergen-specific immunoglobulin E (IgE) antibody production, female BDF(1) mice (60 mice in each group) were exposed to diesel exhaust (particles, 3.24 mg/m(3); nitrogen dioxide, 1.0 ppm: DE group), Kanto loam dust (particles, 3.29 mg/m(3); nitrogen dioxide, 0.01 ppm: KLD group), diesel exhaust without particles (particles, 0.01 mg/m(3); nitrogen dioxide, 1.1 ppm: DEG group), or clean air (pollen and control groups) for 16 h/day, 5 days/wk for 24 wk, as well as to Japanese cedar pollen (JCP) (around 550,000 grains of JCP/m(3)) for 2 days/wk in the same period. The control group was exposed to clean air alone throughout the experiment. The mean values for Japanese cedar pollen allergens (JCPAs)-specific immunoglobulin E (IgE) antibody titers in mice sera measured by enzyme-linked immunosorbent assay (ELISA) in the DE, KLD, and DEG groups were higher than that for the pollen alone group, but not significantly, after both 12 and 24 wk of exposure time. The percentages of animals expressing more than the minimum ELISA titer of JCPAs-specific IgE antibodies in each group were 22% (DE and pollen groups) and 27% (KLD and DEG groups) of the totals at wk 12, and no statistical differences were observed among the groups. However, at wk 24 in the DE, KLD, and DEG groups the responders comprised 73%, 63%, and 67%, respectively, significantly higher than the 33% for the pollen alone group. No significant differences were observed among the DE, KLD, and DEG groups. A slight dose-dependent increase of proliferative responses of mouse cervical lymph node cells to JCPAs in both DE and KLD groups was observed, but not in the DEG group. Remarkable decrease of interferon-gamma and significant increase of interleukin-4 in the nasal lavage fluid were apparent after DE or DEG exposure, but not in the KLD group. These results suggest that these air pollutants (DE, KLD, and DEG) enhance the production of IgE antibodies in mice, with similar adjuvant activities in each case. Furthermore, in the early phase of exposure in which sensitization occurred with exposure to pollen, the fine particles and gas components are considered to have exhibited different enhancing mechanisms in mice as follows: (1) The fine particles augmented production of IgE antibodies through activation of T lymphocytes, and (2) the gas components exhibited almost no action on T lymphocytes, but directly induced disorders of the cytokine network and augmented the production of IgE antibodies.

Air Pollutants↗
PubMed2001

Infrequent frameshift mutations in the simple repeat sequences of hMLH3 in hereditary nonpolyposis colorectal cancers.

BACKGROUND: A recently identified mismatch repair gene, hMLH3, contains two simple repeat sequence regions, (A)9 and (A)8, in its coding region. To clarify the role of hMLH3 in hereditary nonpolyposis colorectal cancer (HNPCC), we searched for hMLH3 somatic and germline mutations, particularly in the repeat regions, in 41 HNPCC patient cells. METHODS: We analyzed the hMLH3 (A)9 and (A)8 repeats in 27 colorectal cancers with microsatellite instability (MSI) as well as in normal cells from 41 HNPCC patients by means of polymerase chain reaction-single-strand conformation polymorphism. hMSH3 (A)8 and hMSH6 (C)8 repeats were also examined in these cancers. RESULTS: Frameshift mutations in the hMLH3 (A)9 repeat were observed in 4/27 (14.8%) cancers with MSI, all of which showed the severe MSI phenotype. No mutations in the (A)8 repeat were found in any case. The mutation frequency of the hMLH3 (A)9 repeat was similar to that of the hMSH6 (C)8 repeat (5/26, 19.2%), but was significantly lower than that of the hMSH3 (A)8 repeat (16/27, 59.3%) (P < 0.001). All four cancers with hMLH3 mutations exhibited germline hMSH2 and/or somatic hMSH3 mutations. No germline mutation in the hMLH3 (A)9 or (A)8 repeat was detected in normal cells from the 41 HNPCC patients. CONCLUSION: hMLH3 mutations were infrequently observed in HNPCC cancers with MSI and they may be secondary to other mismatch repair gene mutations. Hence hMLH3 may only play a small role in HNPCC tumorigenesis.

Adult↗
PubMed2001

The inhibitory effect of dienogest, a synthetic steroid, on the growth of human endometrial stromal cells in vitro.

Dienogest is a synthetic steroid that has been used as a progestogen in contraceptive pills and is currently being studied for its possible clinical use in the treatment of endometriosis. In this study, we investigated the direct effects of dienogest in differentiation and proliferation of human endometrial stromal cells (ESC) in vitro. After 12 days in the presence of oestradiol (10(-8) mol/l) plus dienogest (10(-6) mol/l), cultured ESC underwent morphological differentiation and produced prolactin, a typical marker for decidualization. By using Northern blot analysis and radioimmunoassay, it was shown that treatment of ESC with oestradiol (10(-8) mol/l) plus dienogest (10(-9) to10(-6) mol/l) led to an increase in the levels of prolactin mRNA and prolactin production in a dose-dependent manner. Additionally, RU-486, a progesterone receptor antagonist, almost completely inhibited dienogest-induced prolactin production. As shown by the thymidine uptake method, there was a dose-dependent inhibition of ESC proliferation with dienogest (P < 0.01, control versus concentrations >10(-7) mol/l). The significant inhibition of ESC proliferation by dienogest (10(-7) mol/l) was partially reversed by RU-486 (10(-6) mol/l). In summary, dienogest directly acts on endometrial tissue in progestogenic response, such as decidualization, increased prolactin production and growth retardation. These data imply that dienogest exerts direct effect in suppressing growth of endometriotic implants.

Cell Division↗
PubMed2001

Alkaline-resistance model of subtilisin ALP I, a novel alkaline subtilisin.

The alkaline-resistance mechanism of the alkaline-stable enzymes is not yet known. To clarify the mechanism of alkaline-resistance of alkaline subtilisin, structural changes of two typical subtilisins, subtilisin ALP I (ALP I) and subtilisin Sendai (Sendai), were studied by means of physicochemical methods. Subtilisin NAT (NAT), which exhibits no alkaline resistance, was examined as a control. ALP I gradually lost its activity, accompanied by protein degradation, but, on the contrary, Sendai was stable under alkaline conditions. CD spectral measurements at neutral and alkaline pH indicated no apparent differences between ALP I and Sendai. A significant difference was observed on measurement of fluorescence emission spectra of the tryptophan residues of ALP I that were exposed on the enzyme surface. The fluorescence intensity of ALP I was greatly reduced under alkaline conditions; moreover, the reduction was reversed when alkaline-treated ALP I was neutralized. The fluorescence spectrum of Sendai remained unchanged. The enzymatic and optical activities of NAT were lost at high pH, indicating a lack of functional and structural stability in an alkaline environment. Judging from these results, the alkaline resistance is closely related to the surface structure of the enzyme molecule.

Autolysis↗
PubMed2001

Modulation of reactive oxygen species in endothelial cells by peroxynitrite-treated lipoproteins.

Peroxynitrite has been implicated in the oxidative modification of low-density lipoprotein (LDL) particles, and nitrotyrosine residues in the LDL have been detected in atherosclerotic plaques. Studies have suggested that lipoproteins modified by peroxynitrite lead to the onset of atherosclerotic vascular disease. We therefore prepared in vitro lipoproteins oxidatively modified by peroxynitrite (NO(2)-lipoprotein) and investigated the effect of NO(2)-lipoprotein on the viability of cultured endothelial cells. After exposure of a high-density lipoprotein (HDL) to peroxynitrite, some intermolecular complexes of apolipoproteins in HDL were detected on immunoblotting with monoclonal antibodies against apolipoprotein AI and AII, suggesting that nitration of HDL by peroxynitrite causes intermolecular cross-linking of the apolipoproteins in the particles. Treatment with 1 mM peroxynitrite increased the 3-nitrotyrosine level to 28.5 mmol/mol of tyrosine residues in the prepared NO(2)-HDL, as quantitated by HPLC, and the amount in NO(2)-lipoprotein depended on the peroxynitrite concentration. HDL exhibited a shorter lag phase and the reaction plateaued more rapidly than that with LDL. To clarify whether or not NO(2)-lipoproteins affect the function of endothelial cells, we first examined the viability of cultured human aortic endothelial cells (HAECs) exposed to NO(2)-lipoproteins. Incubation with either NO(2)-HDL or NO(2)-LDL significantly reduced the HAEC viability at 72 h. The results of RT-PCR and Western blotting showed that NO(2)-HDL markedly suppressed at 48 h not only the expressed levels of mRNA and protein but also the activity of catalase in HAECs. In contrast, NO(2)-LDL significantly reduced the expression and activity of Cu(2+),Zn(2+)-superoxide dismutase (CuZn-SOD) in the cells. Neither NO(2)-HDL nor NO(2)-LDL interfered with nitric oxide production or expression of cyclooxygenases and NADPH oxidase in HAECs. Increased radical production in NO(2)-lipoprotein-treated HAECs implied that reactive oxygen species such as superoxide anions and hydroxyl radicals may contribute to the mechanism of the toxic effect induced in endothelial cells by NO(2)-lipoprotein. Overall, NO(2)-lipoprotein may lead to deterioration of the vascular function through these endothelial cell responses.

Arteriosclerosis↗
PubMed2001

Platelet-activating factor acetylhydrolase isoforms I and II in human uterus. Comparisons with pregnant uterus and myoma.

The concentrations of platelet-activating factor (PAF) that possesses the ability to stimulate myometrial contraction are partially regulated by intracellular type of platelet-activating factor acetylhydrolase (PAF-AH) in many tissues. Tissue cytosol contains at least two intracellular PAF-AH, isoforms I and II. To examine the relationship between the activity and isoforms of intracellular PAF-AH in human uterine myometrium and myoma, we assayed the PAF-AH activity and identified the PAF-AH isoforms I and II by Western blot analysis. The intense bands of the alpha2 and ss subunits of PAF-AH isoform I were detected in nonpregnant uterus; however, the specific bands of the alpha1 subunit of PAF-AH isoform I and the PAF-AH isoform II were extremely weak. The levels of the alpha2 and ss subunits and PAF-AH activity in pregnant uterus (37-39 wk gestation) were significantly lower than those in nonpregnant uterus. On the other hand, the level of ss subunit and the PAF-AH activity in myoma were significantly higher than those in nonpregnant uterus. No significant difference was found in the expression of the PAF-AH isoform II among three tissues. These results indicate that the change in the PAF-AH activity observed in pregnant uterus and myoma are due to the lower or higher protein expression of the PAF-AH isoform I, especially the alpha2 and/or ss subunits. The decrease of the uterine PAF-AH activity in the late stage of pregnancy may facilitate the action of PAF to stimulate myometrial contraction.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2001

Intraarterial infusion chemotherapy and radiotherapy with or without surgery for patients with locally advanced or recurrent breast cancer.

We analyzed response, side effects, and local control rates of a multimodal treatment consisting of intraarterial infusion chemotherapy (IAIC) and radiotherapy with or without surgery for patients with locally advanced or recurred breast cancer. Thirty-three patients, clinically diagnosed as stage IIB in 1, IIIA in 2, IIIB in 12, IV in 18, were treated from 1991 to 1998. Twenty-five were primary and eight were recurrent cases after surgery. IAIC started as initial treatment up to three times maximum. In most cases, doxorubicin 50 mg, cisplatin 50 mg, and mitomycin 10 mg were infused in the subclavian and/or internal mammary artery. After IAIC, patients in primary cases underwent radical mastectomy or breast conservation surgery, after radiotherapy at a total dose of 50 Gy/25 fractions/5 weeks with a boost of 10 Gy. In recurrent cases, a full dose of radiotherapy was delivered. Clinical objective and complete response rates were 78% and 9% after IAIC. Despite a high rate of residual positive margin (67%) or clinically residual carcinoma, local recurrence developed only in 2 patients (6%) and local control rates at 5 years were calculated as 89%. Bone marrow suppression was frequent, and skin vesiculation (15%) and ulceration (9%) were experienced after IAIC. Skin ulcer (6%), brachial plexus neuropathy (3%), and radiation pneumonitis (3%) occurred as late toxicity. IAIC was effective as an induction treatment and radiotherapy played a role of local control for patients with locally advanced or recurrent breast cancer.

Adult↗
PubMed2001

Successful treatment of dry eye in two patients with chronic graft-versus-host disease with systemic administration of FK506 and corticosteroids.

PURPOSE: We present two cases of severe dry eye in patients with chronic graft-versus-host disease (CGVHD) after hematopoietic stem cell transplantation (SCT) who were successfully treated by the systemic administration of FK506 and corticosteroids. METHODS AND RESULTS: A 29-year-old man with chronic myelogenous leukemia underwent SCT. Oral and lung CGVHD developed on approximately day 130, and dry eye associated with CGVHD was diagnosed on day 168. The patient began receiving cyclosporin A (150 mg/d) for the treatment of oral and lung CGVHD. Treatment with prednisolone (1 mg/kg/d) began on approximately day 300. Oral and lung GVHD improved slightly, but worsened again although systemic administration of cyclosporin A and prednisolone were continued. Cyclosporin A was discontinued, and systemic administration of FK506 was started on day 376. Forty-four days later, marked improvement in the ocular surface and other organs was observed. However, the dry eye worsened while tapering FK506, with no flare of other affected organs. A 43-year-old woman with myelodysplastic syndrome underwent SCT. She received FK506 for prophylaxis of CGVHD. She had mild dry eye before SCT. Oral and intestinal CGVHD developed, and the dry eye worsened significantly on approximately day 150 while tapering FK506. Treatment with prednisolone (1 mg/kg/d) began, and the dose of FK506 was increased. By day 240, the symptoms of dry eye and the findings of the ocular surface markedly improved, and CGVHD in other organs was completely resolved. However, the improvement in the dry eye was lost when FK506 was tapered for the second time. CONCLUSION: Systemic administration of FK506 with corticosteroids is an effective treatment of severe dry eye in patients with CGVHD, but long-term administration may be required to achieve a lasting response. These cases also suggest that further investigation into the use of topical FK506 and prednisolone as a maintenance therapy should be pursued.

Adult↗
PubMed2001

Recurrent germinoma in the optic nerve: report of two cases.

OBJECTIVE AND IMPORTANCE: Intracranial germinomas often disseminate via the ventricular and subarachnoid pathways, but seeding to the perioptic arachnoid space is extremely unusual. We report two cases of recurrent germinoma seeding in the optic nerve. CLINICAL PRESENTATION: Two men with pure germinoma were initially treated with three cycles of a three-drug regimen of bleomycin, etoposide, and cisplatin, and a complete response was achieved. Patient 1 experienced ventricle wall dissemination 10 months after undergoing the initial treatment and was successfully treated with three cycles of carboplatin and etoposide and then by 24-Gy whole-ventricle radiation. Twelve months later, he complained of progressive visual acuity loss, and magnetic resonance imaging demonstrated bilateral enhancement of the optic nerves. Patient 2 also experienced ventricle wall dissemination 3 months after undergoing the initial chemotherapy, but he exhibited a complete response after undergoing 24-Gy whole-ventricle radiation. Two years later, he complained of progressive visual acuity loss. Magnetic resonance imaging demonstrated bilateral enhancement of the optic nerves and cerebellar hemispheres. INTERVENTION: None of the locations of recurrence were included in the irradiation field, whereas there was no recurrence within the radiation field. Complete responses were obtained with three cycles of a three-drug regimen of ifosfamide, cisplatin, and etoposide and then by 24-Gy whole-brain radiation that included the bilateral optic nerves. The visual acuity of each patient improved slightly. CONCLUSION: Delayed seeding in the optic nerve may result from germinoma cells that remain dormant, so they cannot be destroyed by chemotherapy regimens alone.

Adult↗