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Nozawa K.,Yamamoto Kumiai General Hospital | Nozawa K.,Akita | Sekine A.,Kai Medical | Hozumi S.,Kai Medical | Shimizu T.,Akita University
Psychiatry and Clinical Neurosciences | Year: 2011

The aim of the present 12-week, open-label study was to investigate the effect of olanzapine augmentation in outpatients with depression with melancholic features who demonstrated partial response to standard antidepressants but who were reluctant to change antidepressants. The subjects consisted of 22 outpatients meeting the DSM-IV-TR criteria for major depression. Olanzapine was initially added at 2.5 mg/day and the dose was adjusted according to the clinical condition. Data were analyzed using an intention-to-treat methodology. A paired t-test was used to compare total Montgomery Asberg Depression Rating Scale (MADRS) scores before treatment, at baseline (prior to olanzapine), and 4, 8, and 12 weeks after starting olanzapine. Of 22 enrolled patients, 20 completed the trial. The mean (±SD) MADRS score was 17.1 ± 1.0 at baseline and decreased significantly to 8.1 ± 3.2 at 4 weeks after the administration of olanzapine. This significant reduction continued until 12 weeks, when the mean MADRS score was 4.9 ± 2.9, indicating full remission. These results suggest that olanzapine augmentation may be useful for patients with depression in partial remission. A controlled, double-blind trial, however, is needed to confirm these preliminary findings. © 2011 The Authors. Psychiatry and Clinical Neurosciences.


Nara M.,Akita University | Teshima K.,Akita University | Watanabe A.,Akita University | Ito M.,Akita University | And 8 more authors.
PLoS ONE | Year: 2013

Side population (SP) cells in cancers, including multiple myeloma, exhibit tumor-initiating characteristics. In the present study, we isolated SP cells from human myeloma cell lines and primary tumors to detect potential therapeutic targets specifically expressed in SP cells. We found that SP cells from myeloma cell lines (RPMI 8226, AMO1, KMS-12-BM, KMS-11) express CD138 and that non-SP cells include a CD138-negative population. Serial transplantation of SP and non-SP cells into NOD/Shi-scid IL-2γnul mice revealed that clonogenic myeloma SP cells are highly tumorigenic and possess a capacity for self-renewal. Gene expression analysis showed that SP cells from five MM cell lines (RPMI 8226, AMO1, KMS-12-BM, KMS-11, JJN3) express genes involved in the cell cycle and mitosis (e.g., CCNB1, CDC25C, CDC2, BIRC5, CENPE, SKA1, AURKB, KIFs, TOP2A, ASPM), polycomb (e.g., EZH2, EPC1) and ubiquitin-proteasome (e.g., UBE2D3, UBE3C, PSMA5) more strongly than do non-SP cells. Moreover, CCNB1, AURKB, EZH2 and PSMA5 were also upregulated in the SPs from eight primary myeloma samples. On that basis, we used an aurora kinase inhibitor (VX-680) and a proteasome inhibitor (bortezomib) with RPMI 8226 and AMO1 cells to determine whether these agents could be used to selectively target the myeloma SP. We found that both these drugs reduced the SP fraction, though bortezomib did so more effectively than VX-680 due to its ability to reduce levels of both phospho-histone H3 (p-hist. H3) and EZH2; VX-680 reduced only p-hist. H3. This is the first report to show that certain oncogenes are specifically expressed in the myeloma SP, and that bortezomib effectively downregulates expression of their products. Our approach may be useful for screening new agents with which to target a cell population possessing strong tumor initiating potential in multiple myeloma. © 2013 Nara et al.


Miyakoshi N.,Akita University | Miyakoshi N.,Akita | Aizawa T.,Akita | Sasaki S.,Higashinaruse National Health Insurance Clinic | And 13 more authors.
Journal of Bone and Mineral Metabolism | Year: 2015

Atypical femoral fracture (AFF) often appears with bisphosphonate use. Teriparatide (TPTD) treatment may promote AFF healing, but few controlled or comparative studies have examined the effects of TPTD on healing of bisphosphonate-associated AFF. We retrospectively reviewed the medical records of 45 consecutive AFFs in 34 Japanese patients who had received oral bisphosphonates (alendronate or risedronate) for osteoporosis before AFF and had been followed for ≥12 months (range, 12–90 months). Thirty-seven complete or incomplete AFFs (82 %) were treated surgically and eight incomplete AFFs (18 %) were treated conservatively. Bisphosphonates were stopped at diagnosis. Based on TPTD use after fracture, AFFs were divided into non-TPTD (n = 24) and TPTD (n = 21) groups. Time to fracture-healing and frequency of delayed healing or non-union were compared between groups. Because fracture type (complete or incomplete) differed significantly between groups, only subanalyses for all surgically treated AFFs (complete and incomplete), surgically treated complete AFFs, and conservatively treated incomplete AFFs were performed. In subanalyses for all AFFs treated surgically, mean (± standard deviation) time to fracture healing was significantly better in the TPTD group (5.4 ± 1.5 months) than in the non-TPTD group (8.6 ± 4.7 months; P = 0.012), and the frequency of delayed healing or non-union was significantly lower in the TPTD group than in the non-TPTD group (P = 0.014). Subanalyses for surgically treated complete AFFs yielded similar results, but subanalyses for incomplete AFFs treated conservatively showed no significant differences between groups. TPTD treatment appears to significantly shorten the postoperative time to fracture healing and reduce rates of delayed healing or non-union after bisphosphonate-associated AFF. © 2014, The Japanese Society for Bone and Mineral Research and Springer Japan.


Suzuki M.,Chiba University | Yazawa T.,Chiba University | Ota S.,Chiba University | Morimoto J.,Chiba University | And 9 more authors.
Histopathology | Year: 2015

Aims: High-grade fetal adenocarcinoma (H-FLAC) is a rare variant of pulmonary adenocarcinoma; this study aims to elucidate its clinicopathological features and genetic abnormalities. Methods and results: Clinicopathological, immunohistochemical and mutational analyses were performed on 20 surgically resected lung cancers that showed H-FLAC histology in various proportions. These tumours predominantly occurred in elderly males and in 10 patients who were heavy smokers. Four cases were pure H-FLAC, and 16 cases were mixed H-FLAC, which were found to be combined with conventional-type adenocarcinoma (15 cases), large-cell neuroendocrine carcinoma (three cases), small-cell carcinoma (one case), enteric adenocarcinoma (two cases), choriocarcinoma (two cases), and a solid-clear cell pattern (seven cases). The fetal phenotype and diverse differentiation were supported by the immunoexpression of α-fetoprotein (95%), thyroid transcription factor-1 (TTF-1) (50%), neuroendocrine markers (30-45%), proneural markers (50-69%), and CDX2 (40%). Except for TTF-1 expression (pure H-FLACs, 0%; mixed H-FLACs, 63%), there were no significant differences in histological or immunohistochemical findings between pure and mixed H-FLACs. EGFR, KRAS, BRAF and PIK3CA mutations were identified in 20%, 0%, 0% and 7% of the tumours, respectively. Conclusions: Lung adenocarcinomas with H-FLAC features possess the potential for multidirectional differentiation, and are not strongly associated with known major driver gene mutations. © 2015 John Wiley & Sons Ltd.


Suzuki S.,Akita University | Ishikawa K.,Akita University | Mihara K.,Yamamoto Kumiai General Hospital
Practica Otologica, Supplement | Year: 2010

To clarify laryngeal cancer practices, we followed up 95 cases-92 men and 3 women with a mean age of 66. 3 years between 1990 and 2003. Supraglottic cancer was found in 26. 3% (25 cases), glottic cancer in 71. 6% (68), and subglottic cancer in 2.1% (2). Based on International Union Against Cancer "tumor/node/metastasis" (UICC TNM) classification, a difference exists in glottic and supraglottic distribution. Of glottic cases, 39 (57. 4%) were stage I, 8 (11. 8%) stage II, 10 (14. 7%) stage III, and 11 (16. 2%) stage IV. Of supraglottic cases, 2 (8%) were stage I, 2 (8%) stage II, 4 (16%) stage III, and 17 (68%) stage IV. Cervical lymph node metastasis was detected in 8. 8% of glottic cases and 76. 0% of supraglottic cases. Overall 5-year cumulative crude survival was 74. 5% and cause-specific survival 85. 7%. For glottis cases, 5-year cumulative crude survival was 83. 6% and cause-specific survival 92. 5%. For supraglottic cases, they were 56. 0% and 73. 5%. For stages I-IV, 5-year cause-specific survival was 100%, 87. 5%, 78. 6%, and 80. 0% for glottic cases and 50. 0%, 50. 0%, 75. 0%, and 79. 3% for supraglottic cases.

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