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( Tsuyoshi Hamada ),( Hiroyuki Isayama ),( Yousuke Nakai ),( Osamu Togawa ),( Naminatsu Takahara ),( Rie Uchino ),( Suguru Mizuno ),( Dai Mohri ),( Hiroshi Yagioka ),( Hirofumi Kogure ),( Saburo Matsu 대한소화기학회 2017 Gut and Liver Vol.11 No.1
Background/Aims: In distal malignant biliary obstruction, an antireflux metal stent (ARMS) with a funnel-shaped valve is effective as a reintervention for metal stent occlusion caused by reflux. This study sought to evaluate the feasibility of this ARMS as a first-line metal stent. Methods: Patients with nonresectable distal malignant biliary obstruction were identified between April and December 2014 at three Japanese tertiary centers. We retrospectively evaluated recurrent biliary obstruction and adverse events after ARMS placement. Results: In total, 20 consecutive patients were included. The most common cause of biliary obstruction was pancreatic cancer (75%). Overall, recurrent biliary obstruction was observed in seven patients (35%), with a median time to recurrent biliary obstruction of 246 days (range, 11 to 246 days). Stent occlusion occurred in five patients (25%), the causes of which were sludge and food impaction in three and two patients, respectively. Stent migration occurred in two patients (10%). The rate of adverse events associated with ARMS was 25%: pancreatitis occurred in three patients, cholecystitis in one and liver abscess in one. No patients experienced nonocclusion cholangitis. Conclusions: The ARMS as a first-line biliary drainage procedure was feasible. Because the ARMS did not fully prevent stent dysfunction due to reflux, further investigation is warranted. (Gut Liver 2017;11:142-148)
Yoshifumi Takahashi,Hiroyuki Fujiwara,Kouji Yamamoto,Masashi Takano,Morikazu Miyamoto,Kosei Hasegawa,Maiko Miwa,Toyomi Satoh,Hiroya Itagaki,Takashi Hirakawa,Mayuyo Mori-Uchino,Tomonori Nagai,Yoshinobu 대한부인종양학회 2024 Journal of Gynecologic Oncology Vol.35 No.4
Objective: In Japan, perioperative prophylaxis of pulmonar y embolism (PE) in gynecologiccancer patients with preoperative asymptomatic venous thromboembolism (VTE) has notbeen well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-armclinical trial to investigate the prevention of postoperative symptomatic PE onset by seamlessanticoagulant therapy from the preoperative period to 4 weeks after surger y instead of usingintermittent pneumatic compression. Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosisand stopped preoperatively according to the rules of each institution. Unfractionatedheparin administration was resumed within 12 hours postoperatively, and this was followedby the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle wascontinued for 28 days. Primar y outcome was the occurrence of symptomatic PE in 28 dayspostoperatively. Secondar y outcomes were the incidence of VTE-related events in 28 days and6 months postoperatively and protocol-related adverse events. Results: Between Februar y 2018 and September 2020, 99 patients were enrolled; of these, 82 patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube,or peritoneal cancer; 21 for endometrial cancer; and 3 for cer vical cancer. No symptomatic PEwas obser ved within 28 days postoperatively; two patients had bleeding events (major bleedingand clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increasedalanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). Conclusion: The multifaceted perioperative management for gynecologic malignancies withasymptomatic VTE effectively prevented postoperative symptomatic PE. Trial Registration: JRCT Identifier: jRCTs031180124
( Iwao Saiki ),( Miki Yara ),( Tsuyoshi Yamanaka ),( Hiroyuki Uchino ),( Masato Inazu ) 한국응용약물학회 2020 Biomolecules & Therapeutics(구 응용약물학회지) Vol.28 No.2
Prostate cancer is one of the most common cancers in men. Choline PET or PET/CT has been used to visualize prostate cancer, and high levels of choline accumulation have been observed in tumors. However, the uptake system for choline and the functional expression of choline transporters in prostate cancer are not completely understood. In this study, the molecular and functional aspects of choline uptake were investigated in the LNCaP prostate cancer cell line along with the correlations between choline uptake and cell viability in drug-treated cells. Choline transporter-like protein 1 (CTL1) and CTL2 mRNA were highly expressed in LNCaP cells. CTL1 and CTL2 were located in the plasma membrane and mitochondria, respectively. [<sup>3</sup>H]Choline uptake was mediated by a single Na+-independent, intermediate-affinity transport system in the LNCaP cells. The anticancer drugs, flutamide and bicalutamide, inhibited cell viability and [3H]choline uptake in a concentration-dependent manner. The correlations between the effects of these drugs on cell viability and [3H]choline uptake were significant. Caspase-3/7 activity was significantly increased by both flutamide and bicalutamide. Furthermore, these drugs decreased CTL1 expression in the prostate cancer cell line. These results suggest that CTL1 is functionally expressed in prostate cancer cells and are also involved in abnormal proliferation. Identification of this CTL1-mediated choline transport system in prostate cancer cells provides a potential new therapeutic target for the treatment of this disease.
Fumiaki Nagashima,Ryohta Nishiyama,Beniko Iwao,Yuiko Kawai,Chikanao Ishii,Tsuyoshi Yamanaka,Hiroyuki Uchino,Masato Inazu 한국응용약물학회 2018 Biomolecules & Therapeutics(구 응용약물학회지) Vol.26 No.4
In this study, we examined the molecular and functional characterization of choline uptake in the human esophageal cancer cells. In addition, we examined the influence of various drugs on the transport of [3H]choline, and explored the possible correlation between the inhibition of choline uptake and apoptotic cell death. We found that both choline transporter-like protein 1 (CTL1) and CTL2 mRNAs and proteins were highly expressed in esophageal cancer cell lines (KYSE series). CTL1 and CTL2 were located in the plasma membrane and mitochondria, respectively. Choline uptake was saturable and mediated by a single transport system, which is both Na+-independent and pH-dependent. Choline uptake and cell viability were inhibited by various cationic drugs. Furthermore, a correlation analysis of the potencies of 47 drugs for the inhibition of choline uptake and cell viability showed a strong correlation. Choline uptake inhibitors and choline deficiency each inhibited cell viability and increased caspase-3/7 activity. We conclude that extracellular choline is mainly transported via a CTL1. The functional inhibition of CTL1 by cationic drugs could promote apoptotic cell death. Furthermore, CTL2 may be involved in choline uptake in mitochondria, which is the rate-limiting step in S-adenosylmethionine (SAM) synthesis and DNA methylation. Identification of this CTL1- and CTL2-mediated choline transport system provides a potential new target for esophageal cancer therapy.
Nagashima, Fumiaki,Nishiyama, Ryohta,Iwao, Beniko,Kawai, Yuiko,Ishii, Chikanao,Yamanaka, Tsuyoshi,Uchino, Hiroyuki,Inazu, Masato The Korean Society of Applied Pharmacology 2018 Biomolecules & Therapeutics(구 응용약물학회지) Vol.26 No.4
In this study, we examined the molecular and functional characterization of choline uptake in the human esophageal cancer cells. In addition, we examined the influence of various drugs on the transport of [$^3H$]choline, and explored the possible correlation between the inhibition of choline uptake and apoptotic cell death. We found that both choline transporter-like protein 1 (CTL1) and CTL2 mRNAs and proteins were highly expressed in esophageal cancer cell lines (KYSE series). CTL1 and CTL2 were located in the plasma membrane and mitochondria, respectively. Choline uptake was saturable and mediated by a single transport system, which is both $Na^+$-independent and pH-dependent. Choline uptake and cell viability were inhibited by various cationic drugs. Furthermore, a correlation analysis of the potencies of 47 drugs for the inhibition of choline uptake and cell viability showed a strong correlation. Choline uptake inhibitors and choline deficiency each inhibited cell viability and increased caspase-3/7 activity. We conclude that extracellular choline is mainly transported via a CTL1. The functional inhibition of CTL1 by cationic drugs could promote apoptotic cell death. Furthermore, CTL2 may be involved in choline uptake in mitochondria, which is the rate-limiting step in S-adenosylmethionine (SAM) synthesis and DNA methylation. Identification of this CTL1- and CTL2-mediated choline transport system provides a potential new target for esophageal cancer therapy.