Selective Cyclooxygenase-2 Inhibitor Prevents Cisplatin-induced Tumorigenesis in A/J Mice

Cisplatin is used to treat lung cancer;however, it is also a known carcinogen. Cyclooxygenase-2 (COX-2) inhibitors have been shown to prevent carcinogen-induced experimental tumors. We investigated the effect of a COX-2 inhibitor, celecoxib, on cisplatin-induced lung tumors. One hundred twenty 4-week-old A/J mice were divided into 6 groups:group 1, no treatment;group 2, low-dose celecoxib (150mg/kg);group 3, high-dose celecoxib (1,500mg/kg);group 4, cisplatin alone;group 5, cisplatin plus low-dose celecoxib;and group 6, cisplatin plus high-dose celecoxib. Mice in groups 4-6 were administered cisplatin (1.62mg/kg, i.p.) once a week for 10 weeks between 7 and 16 weeks of age. All mice were sacrificed at week 30. Tumor incidence was 15.8% in group 1, 25% in group 2, 26.3% in group 3, 60% in group 4, 50% in group 5, and 50% in group 6. Tumor multiplicity was 0.2, 0.3, 0.3, 1.3, 1.0, and 0.6 in groups 1-6, respectively. Tumor multiplicity in the cisplatin-treated mice was reduced by celecoxib treatment in a dose-dependent manner (p＜0.05, group 4 vs. group 6). Celecoxib significantly reduced COX-2 expression in cisplatin-induced tumors (p＜0.01, group 4 vs. group 6)

Immunohistochemical detection of P-glycoprotein and carcinoembryonic antigen in small cell lung cancer: with reference to predictability of response to chemotherapy.

In an attempt to elucidate the tumor properties relating to responsiveness to chemotherapy, we examined immunohistochemically the expression of P-glycoprotein (P-gp) and carcinoembryonic antigen (CEA) in small cell lung cancer (SCLC) tumors. Tumor specimens from 33 patients were obtained at the time of diagnosis and relapse. Four patients expressed P-gp in their initial tumors, and 7 others did in recurrent tumors. The overall response rate to chemotherapy of the initial tumors was 75% for P-gp-positive initial tumors and 86% for P-gp-negative tumors, whereas the disease-free and overall survival times were significantly shorter in the former than the latter. Three patients showed CEA in their initial tumors, and 5 others did in recurrent tumors. The patients with CEA-positive initial tumors tended to relapse earlier than those with CEA-negative tumors. In addition, recurrent tumors expressing CEA were resistant to salvage chemotherapy. A clear correlation between CEA expression by tumors and the CEA level in the serum was observed at diagnosis as well as at relapse. These findings indicate that P-gp and/or CEA expression by a tumor and elevated CEA level in the serum may predict refractoriness of the tumor to chemotherapy.</p

Phase II study of ifosfamide, cisplatin, and vindesine combination in advanced non-small cell lung cancer.

Twenty-seven previously untreated patients with unresectable non-small cell lung cancer were treated with a 3-drug combination of ifosfamide, cisplatin, and vindesine as a phase II study. Patients received ifosfamide, 1.3g/m2, on days 1 to 5; cisplatin, 20mg/m2, on days 1 to 5; and vindesine, 3mg/m2, on days 1 and 8; with a sufficient parenteral hydration. Courses were repeated every 4 weeks. Twenty males and seven females with a median age of 61 years were treated and fully evaluated. Five patients had stage IIIA, seven had stage IIIB, and 15 had stage IV disease. One patient with adenocarcinoma achieved a complete response and 16 achieved a partial response, for an overall response rate of 63% (95% confidence limit: 45% to 81%). The median duration of response was 34 weeks (range: 9 to 52 weeks). The median survival time was 58 weeks for patients with IIIA/B disease, and 33 weeks for those with IV disease. The major toxicity was myelosuppression, however, it was generally well-tolerated. These results indicate that the 3-drug combination is active against non-small cell lung cancer and warrants further clinical trials.</p

Survey of Period Variations of Superhumps in SU UMa-Type Dwarf Novae

We systematically surveyed period variations of superhumps in SU UMa-type dwarf novae based on newly obtained data and past publications. In many systems, the evolution of superhump period are found to be composed of three distinct stages: early evolutionary stage with a longer superhump period, middle stage with systematically varying periods, final stage with a shorter, stable superhump period. During the middle stage, many systems with superhump periods less than 0.08 d show positive period derivatives. Contrary to the earlier claim, we found no clear evidence for variation of period derivatives between superoutburst of the same object. We present an interpretation that the lengthening of the superhump period is a result of outward propagation of the eccentricity wave and is limited by the radius near the tidal truncation. We interpret that late stage superhumps are rejuvenized excitation of 3:1 resonance when the superhumps in the outer disk is effectively quenched. Many of WZ Sge-type dwarf novae showed long-enduring superhumps during the post-superoutburst stage having periods longer than those during the main superoutburst. The period derivatives in WZ Sge-type dwarf novae are found to be strongly correlated with the fractional superhump excess, or consequently, mass ratio. WZ Sge-type dwarf novae with a long-lasting rebrightening or with multiple rebrightenings tend to have smaller period derivatives and are excellent candidate for the systems around or after the period minimum of evolution of cataclysmic variables (abridged).Comment: 239 pages, 225 figures, PASJ accepte

独自開発したシート状脂肪幹細胞を用いた特発性大腿骨頭壊死症に対する治療法の開発

金沢大学附属病院Adipose tissue-derived somatic stem cell (ADSC) culture and sheet preparation were possible. The use of white rabbits to create a necrotic femoral head model was also possible, but the extent of necrosis varied, and there was no statistically significant difference in the degree of necrosis regeneration between the groups using ADSCs and ADSC sheets. The variability of the necrosis area in the necrosis modeling process may also have contributed to the variability of the results. We investigated the regeneration process of cartilage defects in a white rabbit osteoarthritis model, which we thought would reduce the variability of the model, and obtained results suggesting that the ADSC sheet may contribute to cartilage regeneration.脂肪組織由来体性幹細胞（ADSC）の培養、シート作成に関しては、再現性の高いものとなった。白色家兎を使用した大腿骨頭壊死モデルの作成も可能であったが、壊死範囲にはばらつきが生じていた。ADSCとADSCシートを用いた群間では、壊死の再生程度において統計学的に有意といえる差までは認めなかった。壊死モデル作成において、壊死領域にもばらつきが生じやすく、その点も結果のばらつきにつながったと考えられた。モデルのばらつきが小さくなると考えて、白色家兎を用いた変形性関節症モデルを作成し、軟骨欠損の再生過程について調査した。ADSCシートが軟骨再生に寄与するのではないかと示唆される結果を得た。研究課題/領域番号:20K17992, 研究期間(年度):2020-04-01 – 2022-03-31出典：研究課題「独自開発したシート状脂肪幹細胞を用いた特発性大腿骨頭壊死症に対する治療法の開発」課題番号20K17992（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-20K17992/20K17992seika/）を加工して作

A proposed new rotating reference axis for the tibial component after proximal tibial resection in total knee arthroplasty.

PURPOSE:During total knee arthroplasty, few rotating reference axes can be reliably used after tibial resection. We speculated that a line that passes through the lateral edge of the posterior cruciate ligament (PCL) at its tibial attachment after resection and the most prominent point of the tibial tubercle [after-tibial resection (ATR) line] will provide a good reference axis. In this study, we aimed to evaluate the association between ATR and Akagi's lines. MATERIALS AND METHODS:In this case-control simulation study, we retrospectively evaluated 38 patients with varus knee and 28 patients with valgus knee. We defined the reference cutting plane as 10 mm distal from the lateral articular surface of the tibia in varus group and as 7 mm distal from the medial articular surface in the valgus group. We measured angles between Akagi's line and the ATR line (ATR line angle) as well as between Akagi's line and 1/3 Akagi's line (1/3 Akagi's line angle), which passes through the midpoint of PCL and the medial third of the patellar tendon. We used paired t-tests to determine the significance of differences between these angles, with p < 0.05 indicating statistical significance. Intra- and interclass correlation coefficients for the reproducibility of 1/3 Akagi's line angle and ATR line angle were analyzed by two surgeons. RESULTS:We found that 1/3 Akagi's line angle was 10.2° ± 1.3° in the varus group and 10.9° ± 1.3° in the valgus group (p = 0.017). The ATR line was positioned externally compared with Akagi's line in all patients. Mean ATR line angles at 0°, 3° and 7° posterior slopes were 6.1° ± 1.9°, 5.8° ± 2.0° and 6.0° ± 1.7° in the varus group and 6.3° ± 2.3°, 6.2° ± 2.3° and 5.4° ± 2.1° in the valgus group, respectively. There were no significant differences in the ATR line angle between the varus and valgus groups. (p = 0.34-0.67) Intra- and interclass correlation coefficients for the reproducibility of 1/3 Akagi's line angle were 0.936 and 0.986 and those for the reproducibility of ATR line angle were 0.811 and 0.839. CONCLUSIONS:The ATR line was positioned between Akagi's line and 1/3 Akagi's line in all patients and was a valid option for evaluating rotational tibial alignment after tibial resection

Effect of a Cyclooxygenase-2 Inhibitor in Combination with (−)-Epigallocatechin Gallate or Polyphenon E on Cisplatin-Induced Lung Tumorigenesis in A/J Mice

We investigated the effects of celecoxib combined with (−)-epigallocatechin-3-gallate (EGCG) or polyphenon E in a cisplatin-induced lung tumorigenesis model. Four-week-old female A/J mice were divided into seven groups: (i) Control, (ii) 150 mg/kg celecoxib (150Cel), (iii) 1,500 mg/kg celecoxib (1500Cel), (iv) EGCG+150 mg/kg celecoxib (EGCG+150Cel), (v) EGCG+1,500 mg/kg celecoxib (EGCG+1500Cel), (vi) polyphenon E+150 mg/kg celecoxib (PolyE+150Cel), and (vii) polyphenon E+1,500 mg/kg celecoxib (PolyE+1500Cel). All mice were administered cisplatin (1.62 mg/kg of body weight, i.p.) 1×/week for 10 weeks and sacrificed at week 30; the numbers of tumors on the lung surface were then determined. The tumor incidence and multiplicity (no. of tumors/mouse, mean±SD) were respectively 95% and 2.15±1.50 in Control, 95% and 2.10±1.29 in 150Cel, 86% and 1.67±1.20 in 1500Cel, 71% and 1.38±1.24 in EGCG+150Cel, 67% and 1.29±1.38 in EGCG+1500Cel, 80% and 1.95±1.36 in PolyE+150Cel, and 65% and 1.05±0.10 in PolyE+1500Cel. The combination of high-dose celecoxib with EGCG or polyphenon E significantly reduced multiplicity in cisplatin-induced lung tumors