Functional expression of choline transporter-like protein 1 (CTL1) in small cell lung carcinoma cells: A target molecule for lung cancer therapy

AbstractCholine is essential for the synthesis of the major membrane phospholipid phosphatidylcholine and the neurotransmitter acetylcholine (ACh). Elevated levels of choline and up-regulated choline kinase activity have been detected in cancer cells. Thus, the intracellular accumulation of choline through choline transporters is the rate-limiting step in phospholipid metabolism and a prerequisite for cancer cell proliferation. However, the uptake system for choline and the functional expression of choline transporters in lung cancer cells are poorly understood. We examined the molecular and functional characterization of choline uptake in the small cell lung carcinoma cell line NCI-H69. Choline uptake was saturable and mediated by a single transport system. Interestingly, removal of Na+ from the uptake buffer strongly enhanced choline uptake. This increase in choline uptake under the Na+-free conditions was inhibited by dimethylamiloride (DMA), a Na+/H+ exchanger (NHE) inhibitor. Various organic cations and the choline analog hemicholinium-3 (HC-3) inhibited the choline uptake and cell viability. A correlation analysis of the potencies of organic cations for the inhibition of choline uptake and cell viability showed a strong correlation (R=0.8077). RT-PCR revealed that choline transporter-like protein 1 (CTL1) mRNA and NHE1 are mainly expressed. HC-3 and CTL1 siRNA inhibited choline uptake and cell viability, and increased caspase-3/7 activity. The conversion of choline to ACh was confirmed, and this conversion was enhanced under Na+-free conditions, which in turn was sensitive to HC-3. These results indicate that choline uptake through CTL1 is used for ACh synthesis. Both an acetylcholinesterase inhibitor (eserine) and a butyrylcholinesterase inhibitor (ethopropazine) increased cell proliferation, and these effects were inhibited by 4-DAMP, a mAChR3 antagonist. We conclude that NCI-H69 cells express the choline transporter CTL1 which uses a directed H+ gradient as a driving force, and its transport functions in co-operation with NHE1. This system primarily supplies choline for the synthesis of ACh and secretes ACh to act as an autocrine/paracrine growth factor, and the functional inhibition of CTL1 could promote apoptotic cell death. Identification of this new CTL1-mediated choline transport system provides a potential new target for therapeutic intervention

Microtensile Bond Strength of Self-Adhesive Luting Cements to Ceramics

The purpose of this paper was to compare the bond strengths of the self-adhesive luting cements between ceramics and resin cores and examine their relation to the cement thickness. Three self-adhesive luting cements (Smartcem, Maxcem, and G-CEM) and a resin cement (Panavia F 2.0) for control were used in the paper. The thickness of the cements was controlled in approximately 25, 50, 100, or 200 μm. Each 10 specimens were made according to the manufacturers' instructions and stored in water at 37°C. After 24 hours, microtensile bond strength (μTBS) was measured. There were significant differences in cements. Three self-adhesive cements showed significantly lower μTBSs than control that required both etching and priming before cementation (Tukey, P < 0.05). The cement thickness of 50 or 100 μm tended to induce the highest μTBSs for each self-adhesive luting cements though no difference was found

Bipolar Hip Arthroplasty Using a Conjoined Tendon-preserving Posterior Approach in Geriatric Patients

In bipolar hemiarthroplasty (BHA), it is important to preserve soft tissue to reduce the risk of postoperative dislocation. A variety of surgical approaches for BHA are available, but extra care is needed with muscle- and tendon-preserving approaches in geriatric patients. We investigated the usefulness of BHA using a conjoined tendon-preserving posterior (CPP) approach, in which only the external obturator muscle is dissected, in geri-atric patients. We retrospectively analyzed the cases of 40 femoral neck fracture patients (10 men, 30 women) aged ≥ 80 years who underwent BHA using the CPP approach. The patients’ average age was 85.8 years (80-94 years). We examined the operation time, bleeding, preservation of short external rotator muscles, complica-tions, and stem alignment and subsidence from postoperative radiographs. Although gemellus inferior muscle injury was detected in 4 patients (10%), the hip joint stability was very excellent in all cases. There was no intraoperative fracture or postoperative dislocation. On postoperative radiographs, all femoral stems were in a neutral position. There was no stem subsidence in all 40 patients. BHA using the CPP approach appeared to be useful even in geriatric patients

An accelerometer-based navigation system provides acetabular cup orientation accuracy comparable to that of computed tomography-based navigation during total hip arthroplasty in the supine position

Background Inadequate acetabular component orientation is associated with postoperative impingement, dislocation, and accelerated polyethylene wear. Computed tomography (CT)-based navigation systems provide accuracy for total hip arthroplasty (THA) but are not available in all facilities. Accelerometer-based navigation systems are inexpensive, but their accuracy remains undetermined. This study compares the accuracy of cup orientation in THA using CT-based and accelerometer-based navigation systems. Methods This retrospective study included 35 consecutive patients (11 males, 24 females; mean age, 65 years) who underwent primary cementless THA via an anterolateral approach in the supine position. Both CT-based and accelerometer-based navigation systems were used simultaneously. The accuracy of cup orientation was compared between the two systems using postoperative CT. Results The accuracy of cup inclination was 2.7° ± 2.0° in the CT-based group and 3.3° ± 2.4° in the accelerometer-based group. The accuracy of cup anteversion was 2.8° ± 2.6° in the CT-based group and 3.4° ± 2.2° in the accelerometer-based group. No significant difference was observed in cup inclination (p = 0.29) or cup anteversion (p = 0.34) between CT-based and accelerometer-based navigation. Conclusions The accuracy of cup positioning did not differ significantly between CT-based and accelerometer-based navigation systems

An accelerometer-based navigation system provides acetabular cup orientation accuracy comparable to that of computed tomography-based navigation during total hip arthroplasty in the supine position

Background Inadequate acetabular component orientation is associated with postoperative impingement, dislocation, and accelerated polyethylene wear. Computed tomography (CT)-based navigation systems provide accuracy for total hip arthroplasty (THA) but are not available in all facilities. Accelerometer-based navigation systems are inexpensive, but their accuracy remains undetermined. This study compares the accuracy of cup orientation in THA using CT-based and accelerometer-based navigation systems. Methods This retrospective study included 35 consecutive patients (11 males, 24 females; mean age, 65 years) who underwent primary cementless THA via an anterolateral approach in the supine position. Both CT-based and accelerometer-based navigation systems were used simultaneously. The accuracy of cup orientation was compared between the two systems using postoperative CT. Results The accuracy of cup inclination was 2.7° ± 2.0° in the CT-based group and 3.3° ± 2.4° in the accelerometer-based group. The accuracy of cup anteversion was 2.8° ± 2.6° in the CT-based group and 3.4° ± 2.2° in the accelerometer-based group. No significant difference was observed in cup inclination (p = 0.29) or cup anteversion (p = 0.34) between CT-based and accelerometer-based navigation. Conclusions The accuracy of cup positioning did not differ significantly between CT-based and accelerometer-based navigation systems

Simple one step syntheses of indole-3-acetonitriles from indole-3-carboxaldehydes

金沢大学大学院自然科学研究科生理活性物質科学金沢大学薬学部One step conversion method of indole-3-carboxaldehydes into indole-3-acetonitriles is developed. Applying the method, 4-nitro- (7 a), 4-phenyl-(7 b), 4-iodo- (7 c), 4-methoxy- (7 d), and 4-benzyloxyindole-3-acetonitrile (7 e) are available in two steps from indole-3-carboxaldehyde (4)