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Persistent CXCR4 expression after preoperative chemoradiotherapy predicts early recurrence and poor prognosis in esophageal cancer

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World Journal of Gastroenterology 2006年第47期12卷 7585-7590页

作者： Kenji Koishi Reigetsu Yoshikawa Tohru Tsujimura Tomoko Hashimoto-Tamaoki Syoudou Kojima hidenori yanagi Takehira Yamamura Yoshinori Fujiwara Second Department of Surgery Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Second Department of Surgery Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Institute for Advanced Medical Sciences Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Second Department of Pathology Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Institute for Advanced Medical Sciences Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Department of Genetics Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan

AIM: To study the effect of CXC chemokine receptor-4 (CXCR4) expression on disease progression and prognosis in esophageal cancer. METHODS: CXCR4 expression was evaluated in 37 patients with histologically confirmed esophageal squamous carcinomas (ESCC) undergoing preoperative chemoradiotherapy (CRT) by immunohistochemical staining. RESULTS: Eleven out of 37 ESCC patients showed a pathological complete response (CR) after CRT. CXCR4 protein expression was observed in cell cytoplasms of 13 tumors, and null expression was seen in 13 tumors. Distant recurrence was significantly more common in patients with positive CXCR4 expression (P = 0.0318). After a median follow-up time of 31.6 mo, 19 patients progressed (12 of 19 expressed positive CXCR4) and 11 died (10 of 11 expressed positive CXCR4). Overall survival was significantly correlated with lymph node metastasis (952.1 ± 53.8 d in negative group vs 475.1 ± 56.2 d in positive group, P = 0.023), distant metastasis (874.0 ± 60.4 d in negative group vs 434.9 ± 75.2 d in positive group, P = 0.014) and CRT (811.5 ± 51.2 d in responder group vs 459.6 ± 94.0 d in non-responder group, P = 0.00038) and further with an absence ofCXCR4 expression or no residual tumor (959.8 ± 51.0 d in null expression or no tumor group vs 412.0 ± 57.1 d in positive expression group, P = 0.0001). CONCLUSION: Persistent positive CXCR4 expression is implicated in tumor aggressiveness and poor prognosis in ESCC after CRT, and preoperative CRT may improve the prognosis of ESCC via CXCL12-CXCR4 signaling pathway.

关键词： CXC chemokine receptor-4 Metastasis Chemoradiotherapy Esophageal cancer

Large mucinous cystic neoplasm of the pancreas associated with pregnancy

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World Journal of Gastroenterology 2008年第47期14卷 7252-7255页

作者： Shin-ichi Ikuta Tsukasa Aihara Chiaki Yasui Hiroya Iida hidenori yanagi Masao Mitsunobu Ayako Kakuno Naoki Yamanaka Department of Surgery Meiwa General HospitalHyogo 663-8186Japan Department of Pathology Meiwa General HospitalHyogo 663-8186Japan

Mucinous cystic neoplasms (MCNs) of the pancreas occur mostly in females and are potentially sex hormone-sensitive. However, a MCN occurring during pregnancy is quite rare. A 30-year-old woman in the tenth week of pregnancy was referred to us because of a rapid increase in left hypochondrial distending pain. On ultrasound, the patient had a large intra-abdominal cystic lesion. She was thereafter diagnosed with missed abortion and a computed tomography scan showed that the lesion was a cystic tumor 18 cm in diameter originating from the pancreatic tail. The patient subsequently underwent tumor resection with distal pancreatectomy, sparing the spleen. Histopathological analysis of the specimen revealed a pancreatic MCN with moderate dysplasia. Immunohistochemically, the tumor was positive for both estrogen and progesterone receptors. To our knowledge, this is the first reported case of pancreatic MCN with moderate dysplasia in association with pregnancy. Our case strongly indicates that pancreatic MCN is female-hormone dependent.

关键词： Mucinous cystic neoplasm Pancreatic tumor Pregnancy

Cyclooxygenase-2 expression after preoperative chemoradiotherapy correlates with more frequent esophageal cancer recurrence

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World Journal of Gastroenterology 2007年第16期13卷 2283-2288页

作者： Reigetsu Yoshikawa Yoshinori Fujiwara Kenji Koishi Syoudou Kojima Tomohiro Matsumoto hidenori yanagi Takehira Yamamura Tomoko Hashimoto-Tamaoki Takashi Nishigami Tohru Tsujimura Second Department of Surgery Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Institute for Advanced Medical Sciences Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Second Department of Surgery Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Institute for Advanced Medical Sciences Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Department of Genetics Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Second Department of Pathology Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan

AIM： To investigate the relationship between cycloo- xygenase-2 （COX-2）, and vascular endothelial growth factor （VEGF）, and to determine the clinical significance of this relationship in esophageal cancer patients undergoing chemoradiotherapy （CRT）. METHODS： Immunohistochemical staining was used to evaluate COX-2 and VEGF expression in 40 patients with histologically-confirmed esophageal squamous carcinoma （ESCC） who were undergoing preoperative CRT. RESULTS： Fourteen out of 40 ESCC patients showed a pathological complete response （CR） after CRT. COX-2 and VEGF protein expressions were observed in the cytoplasm of 17 and 13 tumors, respectively, with null expression in 9 and 13 tumors, respectively. COX-2 expression was strongly correlated with VEGF expression （P 〈 0.05）. There were also significant associations between COX-2 expression, tumor recurrence, and lymph-node involvement （P = 0.0277 and P = 0.0095, respectively）. COX-2 expression and VEGF expression had significant prognostic value for disease-free survival （log-rank test; P = 0.0073 and P = 0.0341, respectively）, but not for overall survival, as assessed by univariate analysis. expression correlates with VEGF expression and might be a useful prognostic factor for more frequent tumor recurrence in ESCC patients undergoing neoadjuvant CRT. These findings support the use of anti-angiogenic COX-2 inhibitors in the treatment of ESCC.

关键词： Chemoradiotherapy Cyclooxygenase-2 Esophageal cancer Metastasis Vascular endothelial growth factor

Diffuse gastroduodenitis and pouchitis associated with ulcerative colitis

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World Journal of Gastroenterology 2006年第36期12卷 5913-5915页

作者： Hiroki Ikeuchi Kazutoshi Hori Takashi Nishigami Hiroki Nakano Motoi Uchino Mitsuhiro Nakamura Nobuaki Kaibe Masafumi Noda hidenori yanagi Takehira Yamamura Second Department of Surgery Hyogo College of Medicine Hyogo Japan Department of Gastroenterology Hyogo College of Medicine. Hyogo Japan Second Department of Pathology Hyogo College of Medicine. Hyogo Japan

We experienced a very rare case of ulcerative colitis (UC) accompanied with analogous lesions in the stomach, duodenum, and ileal J -pouch. Ileal J-pouch anal anastomosis was performed on a 29-year old woman in 1996. Six years later, she was admitted again to our hospital because of epigastralgia, nausea, watery diarrhea and low fever. Based on the results of endoscopic examination, we diagnosed it as pouchitis. Moreover, on hypotonic duodenography, expansion of the duodenal bulb and the descending portion were poor. Kerckring folds disappeared with typical lead-pipe appearance. The pathogenesis of the gastric and duodenal lesion in this patient was similar to that of the colonic lesions of UC. For the gastroduodenal lesions in this patient, symptomatic remission was obtained following administration of crushed mesalazine tablets (1500 mg/d) for 14 d with continuous administration of omeprazole. Firstly we used ciprofloxacin to treat pouchitis. On the fifth day, she got a fever because of catheter infection. In the catheter culture, methicillin-resistant Staphylococcus aureus (MRSA) was detected. Therefore we changed ciprofloxacin to vancomycin hydrochloride (Vancomycin?). Vancomycin was very effective, and the stool frequency dramatically improved in three days. Now she continues to take mesalazine, but her condition is stable and there has been no recurrence of pouchitis.

关键词： Ulcerative colitis Pouchitis Gastroduodenal lesions

ECA39 is a novel distant metastasis-related biomarker in colorectal cancer

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World Journal of Gastroenterology 2006年第36期12卷 5884-5889页

作者： Reigetsu Yoshikawa hidenori yanagi Chun-Shen Shen Yoshinori Fujiwara Masafumi Noda Toshihiko Yagyu Makoto Gega Tsutomu Oshima Takehira Yamamura Haruki Okamura Yoshiro Nakano Tomonori Morinaga Tomoko Hashimoto-Tamaoki Second Department of Surgery Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Institute for Advanced Medical Sciences Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Department of Dermatology Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan Department of Genetics Hyogo College of Medicine Nishinomiya Hyogo 663-8501 Japan

AIM: To investigate the possible role of polysaccharide-K (PSK) -related markers in predicting distant metastasis and in the clinical outcome of colorectal cancer (CRC).METHODS: Firstly, we used protein microarrays to analyze the in vitro expression profiles of potential PSK-related markers in the human colorectal adenocarcinoma cell line SW480, which carries a mutant p53 gene. Then, we investigated the clinical implications of these markers in the prognosis of CRC patients. RESULTS: ECA39, a direct target of c-Myc, was identi-fied as a candidate protein affected by the anti-metastat-ic effects of PSK. Immunohistochemistry revealed that ECA39 was expressed at significantly higher levels in tumor tissues with distant metastases compared to those without (P < 0.00001). Positive ECA39 expression was shown to be highly reliable for the prediction of distant metastases (sensitivity: 86.7%, specificity: 90%, posi-tive predictive value: 86.7%, negative predictive value: 90%). A significantly higher cumulative 5-yr disease free survival rate was observed in the ECA39-negative patient group (77.3%) compared with the ECA39-positive patient group (25.8%) (P < 0.05). CONCLUSION: Our results suggest that ECA39 is a dominant predictive factor for distant metastasis in pa-tients with advanced CRC and that its suppression by PSK might represent a useful application of immuno-therapy as part of a program of integrated medicine.

关键词： ECA39 Distant metastasis Colorectal cancer Polysaccharide-K Integrated medicine

Therapeutic potential of stem cells in subarachnoid hemorrhage

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Neural Regeneration Research 2025年第4期20卷 936-945页

作者： Hideki Kanamaru hidenori Suzuki Department of Neurosurgery Mie University Graduate School of MedicineTsuJapan

Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and *** the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm *** may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient *** complications such as brain volume loss and chronic hydrocephalus can further impact *** the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective *** cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable *** review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.

关键词： delayed cerebral ischemia early brain injury matricellular protein neurogenesis stem cell therapy subarachnoid hemorrhage

Challenges for beyond 5G:ultra-densification of radio access network

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通信学报 2020年第11期41卷 1-11页

作者： Fumiyuki Adachi Ryo Takahashi hidenori Matsuo Research Organization of Electrical Communication Tohoku UniversitySendai 980-8577Japan

Ultra-densification of radio access network(RAN)is a key to efficiently support the exponentially growing mobile data traffic in 5 G ***,extremely high frequency band like mm Wave band was utilized to solve the bandwidth shortage ***,untra-dense reusing the same radio resource produced severe *** the mm Wave link was very harsh due to frequent blockage by *** a new RAN architecture needed to be introduced to realize ultra-reliable communications in such a severe radio propagation *** architecture of distributed MIMO based RAN was ***,enhanced interference coordination(e IC)was ***,the effectiveness of distributed MIMO based RAN with e IC by computer simulation was showed.

关键词： 5G advanced systems distributed MIMO radio access network interference coordination cooperative signal transmission

Potential therapeutic molecular targets for blood-brain barrier disruption after subarachnoid hemorrhage

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Neural Regeneration Research 2019年第7期14卷 1138-1143页

作者： Hideki Kanamaru hidenori Suzuki Department of Neurosurgery Mie University Graduate School of Medicine

Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and *** rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial pressure,followed by global cerebral ***-subarachnoid hemorrhage ischemia,tissue injuries as well as extravasated blood components and the breakdown products activate microglia,astrocytes and Toll-like receptor 4,and disrupt blood-brain barrier associated with the induction of many inflammatory and other *** blood-brain barrier is disrupted,brain tissues are directly exposed to harmful blood contents and immune cells,which aggravate brain injuries ***-brain barrier disruption after subarachnoid hemorrhage may be developed by a variety of mechanisms including endothelial cell apoptosis and disruption of tight junction *** molecules and pathways have been reported to disrupt the blood-brain barrier after subarachnoid hemorrhage,but the exact mechanisms remain *** independent and/or interconnected signaling pathways may be involved in blood-brain barrier disruption after subarachnoid *** review provides recent understandings of the mechanisms and the potential therapeutic targets of blood-brain barrier disruption after subarachnoid hemorrhage.

关键词： blood-brain barrier early brain injury endothelial cell subarachnoid hemorrhage tight junction inflammation matricellular protein Toll-like receptor 4 TLR4

Periostin in cerebrovascular disease

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Neural Regeneration Research 2020年第1期15卷 63-64页

作者： Fumihiro Kawakita hidenori Suzuki Department of Neurosurgery Mie University Graduate School of Medicine

Cerebrovascular diseases,which include ischemic and hemorrhagic strokes,remain serious conditions with high mortality and disability worldwide(He et al.,2018).Ischemic stroke accounts for around 80%of all strokes(He et al.,2018).Hemorrhagic stroke consisting of intracerebral hemorrhage and subarachnoid hemorrhage(SAH)occurs less frequently but may cause poorer outcomes than ischemic stroke(Ji et al.,2017;Luo et al.,2018).It is also well known that aneurysmal SAH may have delayed cerebral ischemia(DCI):thus aneurysmal SAH has both characteristics of hemorrhagic and ischemic strokes(Kanamaru et al.,2019).In spite of enormous efforts to improve outcomes,no conclusive treatment exists thus far,once stroke is completed.

关键词： al. hemorrhagic mortality