Tumor-induced lymphangiogenesis in cervical lymph nodes in oral melanoma-bearing mice.

福岡歯科大学2013年

Tumor-induced lymphangiogenesis in cervical lymph nodes in oral melanoma-bearing mice.

福岡歯科大学2013年

Inhibition of influenza virus replication in cultured cells by RNA-cleaving DNA enzyme

AbstractInfluenza virus replication has been effectively inhibited by antisense phosphothioate oligonucleotides targeting the AUG initiation codon of PB2 mRNA. We designed RNA-cleaving DNA enzymes from 10-23 catalytic motif to target PB2-AUG initiation codon and measured their RNA-cleaving activity in vitro. Although the RNA-cleaving activity was not optimal under physiological conditions, DNA enzymes inhibited viral replication in cultured cells more effectively than antisense phosphothioate oligonucleotides. Our data indicated that DNA enzymes could be useful for the control of viral infection

High expression of cancer stem cell markers in cholangiolocellular carcinoma

Purpose Cholangiolocellular carcinoma (CLC) is an extremely rare malignant liver tumor. It is thought to originate from the ductules and/or canals of Hering, where hepatic stem cells (HpSC) are located, but there are few reports on cancer stem cell markers in CLC. Thus, we evaluated the significance of cancer stem cell markers, including CD133, CD44, and EpCAM, in CLC. Methods The subjects of this study were three patients with CLC and one patient with an intermediate type of combined hepatocellular cholangiocarcinoma (CHC). The cancer cell markers, CK7, CK19, and EMA, were evaluated immunohistochemically. Results Histological examination of the CLC revealed morphologically cholangiolar features and immunohistochemical examination revealed positivity for CD133, CD44, and EpCAM. On the other hand, in the intermediate type of CHC, only CD44 was positive, whereas CD133 and EpCAM were negative. Conclusion CLC may have stronger features derived from HpSCs than an intermediate type of CHC

A pet-type robot AIBO-assisted therapy as a day care program for chronic schizophrenia patients

BackgroundAAT (Animal-assisted therapy) was developed to promote human social and emotional functioning as a day care program for psychiatric patients.AimsIn this study, we performed AAT using a pet-type robot, AIBO for schizophrenic patients.Methods After obtaining informed consent, we performed the AIBO-assisted therapy for three schizophrenic (ICD-10, F20.x2) patients (male: 1, female: 2) whose medication did not change over the 8 weeks study period in a ward.Results It was found that the AAT using AIBO may be useful for the patients with negative and general psychopathological symptoms such as “Anxiety” and “Uncooperativeness”.ConclusionWe make use of this result, and we want to develop the AAT program using a pet-type robot, AIBO which may be suitable for Japanese psychiatric patients

Comparison of the effects of forefoot joint-preserving arthroplasty and resection-replacement arthroplasty on walking plantar pressure distribution and patient-based outcomes in patients with rheumatoid arthritis

Purpose: The purpose of this retrospective study is to clarify the difference in plantar pressure distribution during walking and related patient-based outcomes between forefoot joint-preserving arthroplasty and resection-replacement arthroplasty in patients with rheumatoid arthritis (RA). Methods: Four groups of patients were recruited. Group1 included 22 feet of 11 healthy controls (age 48.6 years), Group2 included 36 feet of 28 RA patients with deformed non-operated feet (age 64.8 years, Disease activity score assessing 28 joints with CRP [DAS28-CRP] 2.3), Group3 included 27 feet of 20 RA patients with metatarsal head resection-replacement arthroplasty (age 60.7 years, post-operative duration 5.6 years, DAS28-CRP 2.4), and Group4 included 34 feet of 29 RA patients with metatarsophalangeal (MTP) joint-preserving arthroplasty (age 64.6 years, post-operative duration 3.2 years, DAS28-CRP 2.3). Patients were cross-sectionally examined by F-SCAN II to evaluate walking plantar pressure, and the self-administered foot evaluation questionnaire (SAFE-Q). Twenty joint-preserving arthroplasty feet were longitudinally examined at both pre- and post-operation. Results: In the 1st MTP joint, Group4 showed higher pressure distribution (13.7%) than Group2 (8.0%) and Group3 (6.7%) (P<0.001). In the 2nd-3rd MTP joint, Group4 showed lower pressure distribution (9.0%) than Group2 (14.5%) (P<0.001) and Group3 (11.5%) (P<0.05). On longitudinal analysis, Group4 showed increased 1st MTP joint pressure (8.5% vs. 14.7%; P<0.001) and decreased 2nd-3rd MTP joint pressure (15.2% vs. 10.7%; P<0.01) distribution. In the SAFE-Q subscale scores, Group4 showed higher scores than Group3 in pain and pain-related scores (84.1 vs. 71.7; P<0.01) and in shoe-related scores (62.5 vs. 43.1; P<0.01). Conclusions: Joint-preserving arthroplasty resulted in higher 1st MTP joint and lower 2nd-3rd MTP joint pressures than resection-replacement arthroplasty, which were associated with better patient-based outcomes.Ebina K., Hirao M., Takagi K., et al. (2017) Comparison of the effects of forefoot joint-preserving arthroplasty and resection-replacement arthroplasty on walking plantar pressure distribution and patient-based outcomes in patients with rheumatoid arthritis. PLoS ONE 12(8): e0183805. doi: 10.1371/journal.pone.0183805

Comparison of the effects of denosumab between a native vitamin D combination and an active vitamin D combination in patients with postmenopausal osteoporosis

The aim of this 12-month, retrospective study was to compare the effects of denosumab (DMAb; 60 mg subcutaneously every 6 months) plus native vitamin D (VD) (cholecalciferol) combination therapy with DMAb plus active VD analog (alfacalcidol) combination therapy in patients with postmenopausal osteoporosis. Patients [N = 127; mean age 75.6 years (range 58–93 years); 28 treatment-naïve patients, 59 patients treated with oral bisphosphonate therapy, 40 patients treated with teriparatide daily] were allocated to either (1) the DMAb plus native VD group (n = 60; cholecalciferol, 10 μg, plus calcium, 610 mg/day; 13 treatment-naïve patients, 28 patients treated with oral bisphosphonate therapy, and 19 patients treated with teriparatide daily) or (2) the DMAb plus active VD group [n = 67; alfacalcidol, 0.8 ± 0.0 μg, plus calcium, 99.2 ± 8.5 mg/day; 15 treatment-naïve patients, 31 patients treated with oral bisphosphonate therapy, and 21 patients treated with teriparatide daily) on the basis of each physician’s decision. Changes in bone mineral density (BMD), serum bone turnover marker levels, and fracture incidence were monitored every 6 months. There were no significant differences in baseline age, BMD, bone turnover marker levels, and prior treatments between the two groups. After 12 months, compared with the DMAb plus native VD group, the DMAb plus active VD group showed similar increases in the BMD of the lumbar spine (6.4% vs 6.5%) and total hip (3.3% vs 3.4%), but significantly greater increases in the BMD of the femoral neck (1.0% vs 4.9%, P < 0.001) and the distal part of the forearm (third of radius) (−0.8% vs 3.9%, P < 0.01). These tendencies were similar regardless of the differences in the prior treatments. The rates of decrease of bone turnover marker levels were similar for tartrate-resistant acid phosphatase isoform 5b (−49.0% vs −49.0%), procollagen type I N-terminal propeptide (−45.9% vs −49.3%), and undercarboxylated osteocalcin (−56.0 vs −66.5%), whereas serum intact parathyroid hormone levels were significantly lower in the DMAb plus active VD group (47.6 pg/mL vs 30.4 pg/mL, P < 0.001). The rate of hypocalcemia was 1.7% in the DMAb plus native VD group and 1.5% in the DMAb plus active VD group, and the rate of clinical fracture incidence was 8.3% in the DMAb plus native VD group and 4.5% in the DMAb plus active VD group, with no significant difference between the groups. DMAb with active VD combination therapy may be a more effective treatment option than DMAb with native VD combination therapy in terms of increasing BMD of the femoral neck and distal part of the forearm and also maintaining serum intact parathyroid hormone at lower levels.This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s00774-016-0792-5Ebina K., Kashii M., Hirao M., et al. Comparison of the effects of denosumab between a native vitamin D combination and an active vitamin D combination in patients with postmenopausal osteoporosis. Journal of Bone and Mineral Metabolism 35, 571 (2017); https://doi.org/10.1007/s00774-016-0792-5

向精神薬のターゲット部位の遺伝子解析 : セロトニントランスポーター遺伝子多型とパーソナリティおよび痛覚との関連研究

我々はセロトニントランスポーター (5-HTT) 3\u27非翻訳領域 (3\u27UTR) 遺伝子多型の影響, 疼痛感受性個人差の原因, 性格の遺伝要因を解明する一助として5-HTT 3\u27UTR遺伝子多型と痛覚閾値およびパーソナリティとの3つの要因の関連性について調査検討を行った。　181人の健常者を対象に, 5-HTT 3\u27UTR遺伝子多型の判定には制限酵素切断長多型解析法を用い, 痛覚閾値に関しては冷水刺激試験および圧刺激試験を, パーソナリティの測定にはTCI (Temperament and Character Inventory) を行った。　遺伝子多型と痛覚閾値には関連がなかった。遺伝子多型とTCIの相関について, 男性ではST3｛超個人的同一化 (vs. 自己弁別)｝が遺伝子型G/G群で有意に高く, 女性ではST (自己超越性総合点) およびST2｛自己忘却 (vs. 自己意識経験)｝が遺伝子型G/T + T/T群で有意に高かった。痛覚閾値とTCIとの関係について, 男性群で冷水刺激閾値とNS4｛無秩序 (vs. 組織化)｝およびNS (新奇性追求) で負の相関, 女性群で冷水刺激閾値とSD4 (自己受容), C5｛純粋な良心 (vs. 利己主義)｝および圧刺激閾値とSD4 (自己受容) で正の相関が認められた。本研究から5-HTT 3\u27UTR遺伝子多型はCloningerの理論における性格次元に影響を与える可能性がある一方で, 痛覚は5-HTT 3\u27UTR遺伝子多型と関与せず, 一方でパーソナリティの一部と相関関係にある可能性が示唆された。To estimate the genetic factors influencing individual differences in sensitivity to pain, we have examined the associations among serotonin reuptake transporter (5-HTT) 3\u27 UTR gene polymorphism, sensitivity to pain and personality. After the procedures were fully explained and written informed consent was obtained, 5-HTT 3\u27 UTR gene polymorphism was investigated by PCR-RFLP, and personality assessment was performed by means of Temperament and Character Inventory (TCI), and pain threshold by means of cold water and pressure stimulation tests in 181 healthy Japanese volunteers. Males with the T allele (T/T and T/G) showed a significantly lower Self-Transcendence (ST) 3 subdimension score than those without the T allele (G/G). Females with the T allele (T/T and T/G) showed significantly higher ST2 subdimension and ST dimension scores than those without the T allele (G/G). There was no significant relationship between 5-HTT 3\u27 UTR gene polymorphism and pain sensitivity. As for pain sensitivity and TCI, there was low negative correlation between cold water stimulation in males and Novelty Seeking (NS) 4 subdimension and NS, and low positive correlation between cold water stimulation in females and Self-Directedness (SD) 4 subdimension and Cooperativeness (C) 5 subdimension, and between pressure stimulation in females and SD4. It is possible that 5-HTT 3\u27 UTR gene polymorphism may affect the character dimension in the theory of Cloninger, however, 5-HTT 3\u27 UTR gene polymorphism may not be related to the sense of pain, and that there is low correlation between pain and a part of the personality

Effect of histone deacetylase inhibitor in combination with 5-fluorouracil on pancreas cancer and cholangiocarcinoma cell lines

Background : Histone deacetylase (HDAC) is well known to be associated with tumorigenesis through epigenetic regulation, and its inhibitors (HDACIs) induce differentiation and apoptosis of tumor cells. We examined the therapeutic effects of valproic acid (VPA, a HDACI) with a combination of 5-fluorouracil (5-FU) in vitro. Methods : A human pancreas cancer cell line (SUIT-2) and a cholangiocarcinoma cell line (HuCCT1) were used. Cell viabilities were evaluated by a cell proliferation assay. We determined the anticancer effects of VPA combined with 5-FU in these cell lines. Results : Pancreas cancer (SUIT-2) : No effect of 5-FU (1.0 μM) was observed, but 17% and 30% of proliferationinhibitory effects were recognized in a dose of 2.5 or 5.0 μM, respectively. Cell viability was only weakly reduced by VPA (0.5 mM). However, in combination of 5-FU (1.0 μM) with VPA (0.5 mM), 19% of inhibitory effect was observed. Cholangiocarcinoma (HuCCT1) : 5-FU (1.0 μM) did not suppress the cell viability, but 5-FU (2.5 μM) suppressed by 23%. VPA (0.5 mM) did not suppress the cell viability, while VPA (1.0 mM) weakly decreased it by 11%. Combination of 5-FU (1.0 μM) and VPA (0.5 mM) markedly reduced the cell viability by 30%. Conclusion : VPA augmented the anti-tumor effects of 5-FU in cancer cell lines. Therefore, a combination therapy of 5-FU plus VPA may be a promising therapeutic option for patients with pancreas cancer and cholangiocarcinoma