Activation of the α7 nicotinic acetylcholine receptor upregulates blood-brain barrier function through increased claudin-5 and occludin expression in rat brain endothelial cells.

The blood-brain barrier (BBB) is formed by brain endothelial cells (BECs) and regulates brain homeostasis by restricting the entry of blood-borne substances into the brain. Recent in vivo studies have shown that administration of nicotinic acetylcholine receptor (nAChR) agonists protects against BBB disruption and neuroinflammation induced by stroke and traumatic brain injury through the systemic cholinergic anti-inflammatory pathway. In the present study, we focused on the nAChRs expressed on BECs rather than those widely expressed in the central nervous system and peripheral tissues, and examined whether activation of the nAChRs on BECs facilitates BBB function. We used primary cultures of rat brain endothelial cells to evaluate brain endothelial permeability and tight junction (TJ)-related protein expression after a 24-h exposure to PHA543613 (a selective α7 nAChR agonist) or 5-iodo-A-85380 (a selective α4ß2 nAChR agonist). We found that PHA543613 decreased sodium fluorescein permeability and increased the expression levels of claudin-5 and occludin, key TJ components. In contrast, 5-iodo-A-85380 had no effect on brain endothelial permeability or TJ protein expression. These findings suggest that the selective activation of α7 nAChRs on BECs has a specific role in upregulating BBB properties through increased claudin-5 and occludin expression.

[An Analysis of Placement of a Self-Expanding Metallic Stent as Bridge to Surgery for Surgical Resection of Stageâ £ Obstructive Colorectal Cancers].

In our institution, placement of a self-expanding metallic stent (SEMS) for obstructive colorectal cancer to avoid emergency operations, namely as a bridge to surgery (BTS), was introduced in April 2012. Here, we assess the efficacy and safety of pre-operative SEMS placement for treatment of Stage Ⅳ obstructive colorectal cancer. We analyzed a total of 44 cases of Stage Ⅳ colorectal cancer, which consisted of 13 obstructive cases that were surgically resected following SEMS placement as BTS (BTS group), and 31 cases that were resected in elective operations without pre-operative SEMS placement (Ope group), from April 2012 to August 2014. None of the patients had any adverse events during the SEMS procedure or after SEMS placement, and all patients of BTS group could undergo the planned operations after sufficient decompression. In the postoperative period, 1 patient of BTS group (7.7%) had anastomosis bleeding, but no other complications, including anastomosis leakage, were observed in BTS group. However more progressive primary tumors were resected in BTS group (p=0.0115), there were no significant differences for post-operative course between the 2 groups; this indicated avoiding high-risk emergency operations contributed to adequate short-term outcomes in BTS group comparable to those in Ope group. SEMS placement as BTS could be performed safely for Stage Ⅳ obstructive colorectal cancer cases, and was 1 of the effective strategies for local treatment.

[A Case of Ascending Colon Cancer with Extra Iliac Lymph Node Metastases].

We report a case of ascending colon cancer with right extra iliac lymph node metastases. A 60s-year-old woman underwent right hemicolectomy with lymph node dissection in July 2011. Pathological diagnosis was T4 (SE), N1 (2/42), M0, stage ⅢA. Adjuvant chemotherapy with tegafur/uracil was administered after the operation for 6 months. One year after the operation, the serum carcinoembryonic antigen (CEA) level was gradually increasing. Three years after the operation, positron emission tomography-computed tomography (PET-CT) delineated a 3 cm mass with an abnormal signal on the right lower abdominal side of the external iliac vessels. The diagnosis was an isolated remnant tumor in the right extra iliac vessels area from the primary ascending colon cancer. Other recurrent lesions were not found; therefore, resection of this mass was performed. Pathological findings confirmed lymph node metastases from the ascending colon cancer. This type of metastasis is extremely rare, and more case reports are needed to determine the mechanism behind these metastases.

[A Case of Simultaneous Laparoscopic Resection of Sigmoid Colon Cancer and Liver Metastases after Chemotherapy with Modified FOLFOX6 plus Panitumumab].

A 70s-year-old man was referred to our hospital because of sigmoid colon cancer. Computed tomography (CT) revealed a large mass in the right lobe of the liver and small masses in Couinaud segments Ⅳ and Ⅵ. We started systemic chemotherapy with mFOLFOX6 and panitumumab. After 6 courses of the treatment, the size and number of the liver metastases was remarkably reduced on CT. We performed a simultaneous laparoscopic resection for the primary tumor and synchronous liver metastases. The postoperative course was uneventful and he had no signs of recurrence 12 months after surgery.

[A Case of Locally Advanced Rectal Cancer Curatively Resected Following Chemoradiotherapy].

A man in his 70s was referred to our hospital with anorexia, weight loss, and constipation. After examination by computed tomography (CT), magnetic resonance imaging (MRI), and colonoscopy, he was diagnosed as having a locally advanced rectal cancer with abscess formation. Because CT and MRI indicated that the tumor had invaded the seminal vesicle, prostate, and sacrum, we diagnosed it as an unresectable tumor. We treated the abscesses around the tumor by sigmoid colostomy with administration of antibiotics. After control of the infection, the patient received systemic chemotherapy with capecitabine/oxaliplatin (XELOX) plus bevacizumab (BV). After the 5th courses of XELOX plus BV, the primary tumor showed a tendency to shrink, but invasion to the neighboring organs was still seen. Therefore, we treated him with chemoradiotherapy (CRT) using S-1. After completion of CRT with no significant adverse effects, the tumor invasion to the neighboring organs disappeared, and we performed a low anterior resection 9 weeks later. Pathological findings revealed that the tumor had shrunk remarkably and it was resected curatively, although a few tumor cells remained in the subserosal layer of the ulcerative scar caused by the CRT. His postoperative course was uneventful, and he underwent adjuvant chemotherapy with S-1 for 3 months after discharge. To date, no disease recurrence has been detected. We report a case of locally advanced rectal cancer, which was curatively resected following chemoradiotherapy, along with a short literature review.