ハライド系フラックスによる希土類金属の脱酸

希土類金属としてネオジム,プラセオジムを対象とし,ハライド系フラックスとして特にそれらのフッ化物を(NdF_3,PrF_3)を取り上げ研究を行い,以下の知見を得た. 1. 種々のハライド系フラックスによる予備脱酸実験種々のハライド系フラックスを使用して実際に脱酸実験を行い,脱酸効果に対するフラックス種による影響と本法の有効性を確認した. 2. REF_3(RE=Nd,Pr)と平衡する酸素を含む化合物の同定フラックスが溶解する温度の1723Kにおいて,黒鉛坩堝中で溶解したNdF_3あるいはPrF_3中に固体Nd_2O_3あるいは Pr_6O_を浸漬させて反応させた後,急冷して得られた試料をX線回折により分析したところ,両相において,NdOF相あるいは PrOF相の存在を確認した. 3. RE-REF_3-RE_2O_3系状態図の作成 2.の結果を踏まえ1723K,モリブデン坩堝中において,RE-REF_3-REOF系三相平衡実験を行った.この結果とこれまでに当研究室で得られている本系に関する結果をあわせて,RE-REF_3-RE_2O_3系状態図を作成した.また,作成した状態図をもとに,NdF_3あるいはPrF_3によるネオジム,プラセオジムの脱酸反応を推定した. 4. 脱酸実験ネオジムならびにプラセオジムを対象とし,NdF_3あるいはPrF_3をフラックスとして脱酸実験を行い,推定した脱酸反応の妥当性を確認するとともに,本法が,簡便な脱酸処理であるにもかかわらず,効果的な脱酸方法であることが分かった.科学研究費補助金 研究種目:基盤研究(C)(2) 課題番号:09650806 研究代表者:藤澤 敏治 研究期間:1997-1998年度research repor

Curative remnant total pancreatectomy for recurrent pancreatic acinar cell carcinoma: A case report

application/pdfIntroduction and importance Acinar cell carcinoma （ACC） of the pancreas is a rare pancreatic cancer subtype （incidence, 0.5–2%） with unclear epidemiology and prognosis. Sometimes, repeat resection including total pancreatectomy is required for recurrence. We report a case of ACC recurring in the remnant pancreatic head after distal pancreatectomy that was successfully cured by remnant pancreatic resection following combination therapy with nab-paclitaxel （nab-PTX） and gemcitabine （GEM）. Case presentation A 64-year-old woman was referred for pancreatic tumour treatment. CT revealed a 46-mm tumour in the pancreatic body, and endoscopic ultrasonography-guided fine needle aspiration （EUS-FNA） indicated ACC. Distal pancreatectomy was performed, and the final diagnosis was ACC. CT 18 months later showed a 34-mm tumour in the remnant pancreatic head revealed as ACC by EUS-FNA. Portal vein invasion was apparent, so neoadjuvant chemotherapy with nab-PTX and GEM was administered, and remnant pancreatic resection （total pancreatectomy） was performed. No recurrence or distant metastasis was present more than 6 months later. Clinical discussion Mean survival time for ACC is 18–47 months, and prognosis is good compared with pancreatic ductal adenocarcinoma （PDAC）. ACC tends to extend and grow along the main pancreatic duct, which increases the recurrence rate to 50–60%. EUS and EUS-FNA were useful for evaluating tumour extension and diagnosis. Repeat pancreatic resection that included total pancreatectomy was feasible and could be performed safely. Conclusion ACC has a better prognosis than PDAC but with a higher recurrence rate. Aggressive surgical resection that included remnant total pancreatotomy with chemotherapy was useful in treating ACC

Non-Cytotoxic Photodynamic Therapy with Talaporfin Sodium Reduces the Expression of CXCR4 and Enhances Chemotherapeutic Efficacy in Undifferentiated Gastric Cancer Cell Line HGC27

Gastric cancer (GC), particularly the undifferentiated type, is frequently associated with peritoneal metastasis, which significantly worsens prognosis due to its resistance to conventional treatments. Photodynamic therapy (PDT) is localized treatment using a photosensitizer (PS) activated by light of a specific wavelength to generate cytotoxic reactive oxygen species that induce cell death. Severe adverse events were reported from clinical trials investigating PDT for peritoneal dissemination conducted until the early 2000s, leaving its safety and clinical effectiveness unestablished. The present study explored whether “non-cytotoxic” PDT using talaporfin sodium (TS) could enhance efficacy of chemotherapeutic agents in undifferentiated GC cell line HGC27. Cell viability was evaluated with MTT assay following TS-PDT, and the synergistic effect between non-cytotoxic TS-PDT and anticancer drug SN-38 was assessed. Changes in expression of drug resistance markers were analyzed through qRT-PCR, Western blotting, and immunocytochemistry. We found that non-cytotoxic TS-PDT enhanced the efficacy of chemotherapy in the undifferentiated GC cell line and reduced the expression of C-X-C chemokine receptor type 4, a key marker associated with GC stem-like properties. These findings highlight the potential of non-cytotoxic TS-PDT as a synergistic treatment approach. We conclude that non-cytotoxic TS-PDT could enhance drug sensitivity and offers a promising therapeutic strategy for GC

Extracellular Volume Fraction Calculated Using Contrast-Enhanced Computed Tomography as a Biomarker of Oxaliplatin-Induced Sinusoidal Obstruction Syndrome: A Preliminary Histopathological Analysis

Background. Oxaliplatin (OX)-based chemotherapy induces sinusoidal obstruction syndrome (SOS) in the nontumorous liver parenchyma, which can increase the risk of liver resection due to colorectal liver metastasis (CRLM). The extracellular volume (ECV) calculated from contrast-enhanced computed tomography (CT) has been reported to reflect the morphological change of hepatic fibrosis. The present retrospective study aimed to evaluate the ECV fraction as a predictive factor for OX-induced SOS. Methods. Our study included 26 patients who underwent liver resection for CRLM after OX-based chemotherapy with a preoperative dynamic CT of appropriate quality. We investigated the relationship between the pathological SOS grade and the ECV fraction. Results. Overall, 26 specimens from the patients were graded with the SOS classification of Rubbia-Brandt et al. as follows: grade 0, n = 17 (65.4%); grade 1, n = 4 (15.4%); and grade 2, n = 5 (19.2%). No specimens showed grade 3 SOS. In a univariate analysis, the ECV fraction in grade 0 SOS was significantly lower than that in grade 1 + 2 SOS (26.3 ± 3.4% vs. 30.6 ± 7.0%; P = 0.025). The cutoff value and AUC value of the ECV fraction to distinguish between grades 0 and 1 + 2 were 27.5% and 0.771, respectively. Conclusions. Measurement of the ECV fraction was found to be a potential noninvasive diagnostic method for determining early-stage histopathological sinusoidal injury induced by OX-based chemotherapy.Citation: Kai K, Hamada T, Sato Y, Hiyoshi M, Imamura N, Yano K, Ikeda T, Ichihara A, Ogata S, Choijookhuu N, Hishikawa Y, Hosokawa A, Nanashima A. Extracellular Volume Fraction Calculated Using Contrast-Enhanced Computed Tomography as a Biomarker of Oxaliplatin-Induced Sinusoidal Obstruction Syndrome: A Preliminary Histopathological Analysis. J Oncol. 2023 Feb 14;2023:1440257. doi: 10.1155/2023/144025

Relationship between survival outcomes in patients with colorectal liver metastasis undergoing hepatectomy and significance of fibrotic markers for liver injury assessment

Background: Progression of chronic liver dysfunction influenced by long-term chemotherapy or repeated hepatectomy might be related to patient overall survival as well as tumor factors in colorectal liver metastasis (CLM) patients. Our aim of this study was to clarify the relationship between fibrotic liver damage and malignant behaviors of CLM malignancy or its long-term survivals by the retrospective cohort study. Methods: We examined the relationship between tumor-related factors or six liver fibrosis-associated parameters, including platelet count, hyaluronic acid (HA), mac-2 binding protein glycosylation isomer (M2BPGi), type IV collagen 7S (T4C7), aspartate aminotransferase-to-platelet ratio index (APRI), The fibrosis-4 (Fib-4) index, and clinicopathological parameters, surgical records, and postoperative patient survival in the 45 consecutive patients with CLM who underwent radical hepatectomy. Results: Fibrotic parameters were platelet count of 23.0±8.5 ×104/µL, HA level of 68.9±82.3 ng/mL, M2BPGi of 0.87±0.48 ng/mL, and type IV collagen level of 5.74±3.76 ng/mL. Platelet count was significantly correlated with HA level (P<0.05) and tended to be correlated with M2BPGi levels (P=0.056). HA level was significantly associated with albumin level (P<0.05). Overall survival in this series showed five-year overall survivors after hepatectomy in 44 patients (98%), but cancer-related deaths were observed in only one patient. Patients with higher grades and increased bilirubin levels demonstrated significantly lower cancer-free survival (P<0.05), but fibrotic parameters were not associated with prognostic factors. Conclusions: Fibrotic markers indicating chemotherapy or repeated surgical liver injury were not significant predictive factors reflecting cancer malignant behaviors or patient overall survival, contrary to our hypothesis. The current overall survival status using various modalities for cancer recurrence is satisfactory under our present perioperative management

Relationship of immunonutritional factor with changes in liver volume after portal vein embolization

application/pdfBackground To identify predictors of changes in hepatic volumes after portal vein embolization, we examined the relationship with preoperative nutritional and immunological parameters. Patients and Methods Ninety-three patients who underwent portal vein embolization were included. The control group comprised 13 patients who underwent right hepatectomy without portal vein embolization. Computed tomographic volumetric parameter was measured for changes in embolized and nonembolized liver. Correlation with various candidates of immunonutritional parameters was examined. Results Difference in increased liver ratio was 9.1%. C-reactive protein levels significantly increased after portal vein embolization （P  0.92 and increased liver volume ≥ 10% tended to correlate with lower prevalence of severe complications. Only increased intraoperative blood loss ≥ 1,500 mL was significantly associated with morbidity and mortality （P < .05）. Conclusion Contrary to our hypothesis, immunonutritional parameters, except C-reactive protein and C-reactive protein/albumin ratio, did not reflect hypertrophy after portal vein embolization. Although it is difficult to predict the hypertrophic degree, the strategy of scheduled hepatectomy should be switched in case of impaired inflammatory status after portal vein embolization

Pivotal role of High-Mobility Group Box 2 in ovarian folliculogenesis and fertility

BACKGROUND High-Mobility Group Box 1 (HMGB1) and HMGB2 are chromatin-associated proteins that belong to the HMG protein family, and are involved in the regulation of DNA transcription during cell differentiation, proliferation and regeneration in various tissues. However, the role of HMGB2 in ovarian folliculogenesis is largely unknown. METHODS We investigated the functional role of HMGB1 and HMGB2 in ovarian folliculogenesis and fertilization using C57BL/6 wild type (WT) and HMGB2-knockout (KO) mice. Ovarian tissues were obtained from WT and HMGB2-KO mice at postnatal days 0, 3, 7, and 2, 6 months of age, then performed immunohistochemistry, qPCR and Western blotting analyses. Oocyte fertilization capability was examined by natural breeding and in vitro fertilization experiments. RESULTS In HMGB2-KO mice, ovary weight was decreased due to reduced numbers of oocytes and follicles. Natural breeding and in vitro fertilization results indicated that HMGB2-KO mice are subfertile, but not sterile. Immunohistochemistry showed that oocytes expressed HMGB2, but not HMGB1, in neonatal and adult WT ovaries. Interestingly, in HMGB2-KO ovaries, a compensatory increase in HMGB1 was found in oocyte nuclei of neonatal and 2-month-old mice; however, this was lost at 6 months of age. CONCLUSIONS The depletion of HMGB2 led to alterations in ovarian morphology and function, suggesting that HMGB2 plays an essential role in ovarian development, folliculogenesis and fertilization.Citation: Shirouzu S, Sugita N, Choijookhuu N, Yamaguma Y, Takeguchi K, Ishizuka T, Tanaka M, Fidya, Kai K, Chosa E, Yamashita Y, Koshimoto C, Hishikawa Y. Pivotal role of High-Mobility Group Box 2 in ovarian folliculogenesis and fertility. J Ovarian Res. 2022 Dec 20;15(1):133. doi: 10.1186/s13048-022-01071-4. Erratum in: J Ovarian Res. 2023 Jan 24;16(1):21. doi: 10.1186/s13048-023-01105-5

SETDB1-Mediated Chromatin Regulation in Intestinal Epithelial Cells During Intestinal Ischemia-Reperfusion Injury

SET domain bifurcated 1 (SETDB1), a histone H3K9-specific methyltransferase, is crucial for heterochromatin formation and intestinal homeostasis, but its role in intestinal ischemia-reperfusion injury (IRI) remains unclear. This study investigated changes in SETDB1-mediated nuclear chromatin regulation in intestinal epithelial cells (IECs) using an IRI mouse model. Jejunal samples were collected after 75 min of ischemia followed by 24 hr of reperfusion. Sinefungin was administered as a histone methyltransferase inhibitor. Morphologic changes were evaluated using hematoxylin-eosin staining and electron microscopy, and cell-adhesion molecule expression, including ZO-1, E-cadherin, integrin-β4, and laminin, was evaluated using immunohistochemistry. Super-resolution microscopy analyzed intranuclear SETDB1 localization and heterochromatin formation in IECs. IRI-affected jejunum exhibited massive IEC detachment, dilated intercellular spaces, basement membrane damage, and decreased expression of E-cadherin and integrin-β4. Sinefungin prevented these changes, however. The proportion of IECs expressing nuclear SETDB1 throughout the euchromatin was significantly higher in IRI-affected jejunum (77.8%) than sham-treated (3.0%) or sinefungin-treated, IRI-affected jejunum (2.7%). The proportion of IECs with decreased heterochromatin was significantly higher in sinefungin-treated, IRI-affected jejunum (84.3%) than untreated IRI-affected jejunum (15.6%). These findings suggest that SETDB1-mediated chromatin regulation is pivotal in intestinal IRI and represents a potential therapeutic target

Rare resected eight cases of duodenal adenocarcinomas.

application/pdfIntroduction: Duodenal adenocarcinoma is a rare malignancy; recently, it has been found to be accompanied by operative indications.Methods: Nine consecutive rare cases were diagnosed with duodenal carcinoma （DC）, in which clinicopathological characteristics were retrospectively examined. Age was ranged over middle-aged males and females. No clinical onset with severe symptoms was observed, and the specific treatment for accompanied diseases or habits was not found.Outcomes: One case of two T1 stage DCs that underwent pancreas-sparing duodenectomy. Stage II DC was diagnosed in three cases, and stage III DC was diagnosed in four cases. Pancreaticoduodenectomy （PD） mainly occurred in seven patients, and duodenectomy was limited in two patients. All operations were safely performed, and the postoperative course showed no severe morbidity. Histological findings showed R0 resection in eight cases and R1 at the retroperitoneal dissecting part in one case. Five patients with advanced-stage DC underwent adjuvant chemotherapy; however, four patients showed tumor recurrence within 12 months. With additional strong chemotherapy, eight patients survived up to 84 months, and one died of liver metastasis at 43 months after surgery. Three representative cases of mucosal invasion with widespread pancreas-sparing duodenectomy and advanced-stage DC cases undergoing duodenectomy or PD are shown.Conclusion: In the field of upper digestive tract surgery, duodenal adenocarcinoma and various applications of surgery or adjuvant chemotherapy for long-term survival are important

Observation of the ηc(2S) in Exclusive B→KKSK-π+ Decays

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