中国の高等教育政策と組織変革：大学発展要因の分析

学位の専攻分野の名称：博士（先端マネジメント）学位記番号：甲経営第42号（文部科学省への報告番号甲第781号）学位授与年月日：2022年３月16

Correlations between Extranodal Metastasis and Prognosis in Patients with Squamous Cell Carcinoma of the Esophagus

Background Extranodal metastasis (EM) has been reported in carcinomas of many organs. However, the clinicopathological significance of EM in squamous cell carcinoma of the esophagus remains unclear, and this study sought to clarify this issue. MethodsThis study included 220 patients who underwent an esophagectomy with lymphadenectomy for primary esophageal carcinoma from 1996 to 2008. EM was defined as the presence of cancer cells in the soft tissue that were discontinuous with the primary lesion, or in the perinodal soft tissue distinct from the lymph nodes. Results EM was detected in 25 (9.6%) of the 220 patients, and in 56 (0.7%) of the 8,186 nodules retrieved as ‘lymph nodes’. The incidence of EM was significantly higher in patients who had tumors of a larger size (diameter ≥ 4 cm), lymphatic vessel invasion, lymph node metastasis, a high pathological stage, infiltrative growth pattern, or a high pT-stage. The 5-year overall survival rates in N0-1 patients with EM were significantly lower than in the patients without EM (P = 0.005). Conclusion EM is closely associated with the development and aggressiveness of esophageal carcinoma, and the presence of EM can be useful for predicting prognosis after surgery in N0-1esophageal carcinoma patients

Sequence-specific DNA binding by long hairpin pyrrole–imidazole polyamides containing an 8-amino-3,6-dioxaoctanoic acid unit

With the aim of improving aqueous solubility, we designed and synthesized five N-methylpyrrole (Py)–N-methylimidazole (Im) polyamides capable of recognizing 9-bp sequences. Their DNA-binding affinities and sequence specificities were evaluated by SPR and Bind-n-Seq analyses. The design of polyamide 1 was based on a conventional model, with three consecutive Py or Im rings separated by a β-alanine to match the curvature and twist of long DNA helices. Polyamides 2 and 3 contained an 8-amino-3, 6-dioxaoctanoic acid (AO) unit, which has previously only been used as a linker within linear Py–Im polyamides or between Py–Im hairpin motifs for tandem hairpin. It is demonstrated herein that AO also functions as a linker element that can extend to 2-bp in hairpin motifs. Notably, although the AO-containing unit can fail to bind the expected sequence, polyamide 4, which has two AO units facing each other in a hairpin form, successfully showed the expected motif and a K[D] value of 16 nM was recorded. Polyamide 5, containing a β-alanine–β-alanine unit instead of the AO of polyamide 2, was synthesized for comparison. The aqueous solubilities and nuclear localization of three of the polyamides were also examined. The results suggest the possibility of applying the AO unit in the core of Py–Im polyamide compounds

Aluminium reduces sugar uptake in tobacco cell cultures: a potential cause of inhibited elongation but not of toxicity

Aluminium is well known to inhibit plant elongation, but the role in this inhibition played by water relations remains unclear. To investigate this, tobacco (Nicotiana tabacum L.) suspension-cultured cells (line SL) was used, treating them with aluminium (50 μM) in a medium containing calcium, sucrose, and MES (pH 5.0). Over an 18 h treatment period, aluminium inhibited the increase in fresh weight almost completely and decreased cellular osmolality and internal soluble sugar content substantially; however, aluminium did not affect the concentrations of major inorganic ions. In aluminium-treated cultures, fresh weight, soluble sugar content, and osmolality decreased over the first 6 h and remained constant thereafter, contrasting with their continued increases in the untreated cultures. The rate of sucrose uptake, measured by radio-tracer, was reduced by approximately 60% within 3 h of treatment. Aluminium also inhibited glucose uptake. In an aluminium-tolerant cell line (ALT301) isogenic to SL, all of the above-mentioned changes in water relations occurred and tolerance emerged only after 6 h and appeared to involve the suppression of reactive oxygen species. Further separating the effects of aluminium on elongation and cell survival, sucrose starvation for 18 h inhibited elongation and caused similar changes in cellular osmolality but stimulated the production of neither reactive oxygen species nor callose and did not cause cell death. We propose that the inhibition of sucrose uptake is a mechanism whereby aluminium inhibits elongation, but does not account for the induction of cell death