Relationship between the laminectomy extension and spinal cord injury caused by acute spinal shortening: goat in vivo experiment.

OBJECTIVE: To investigate the relationship between different types of laminectomy extension and spinal cord injury subsequent to acute spinal shorting after 3-column osteotomy in living goat model. METHODS: A total of 18 healthy goats were selected, and a procedure of bivertebral column resections and total laminectomy of T13 and L1 was completed followed by different laminectomy extensions under the somatosensory evoked potential (SSEP) monitoring. The samples were divided into three groups according to types of subsequent laminectomy extension. In the first group (enlarged resection of upper lamina group), laminectomy extension was performed on 10 mm caudal to T12; in the second group (equidistant enlarged resection of upper and lower lamina group), laminectomy extension was performed on 5 mm caudal to T12 and 5 mm cranial to L2 simultaneously; and in the third group (enlarged resection of lower lamina group), laminectomy extension was performed on 10 mm cranial to L2. The SSEP measured after vertebral resection was set as the baseline, and the SSEP decreased by 50% from the baseline amplitude and/or delayed by 10% relative to the baseline peak latency was set as positive results, which indicated spinal cord injury. Spinal column was gradually shortened until the SSEP monitoring just did not show a positive result. The shortened distance (ΔH) and the changed angle of the spinal cord buckling (Δα) were measured in each group. Neurologic function was recorded by the Tarlov scores at 2 days after the surgery. RESULTS: The safe shortening distances of three groups were 38.6 ± 1.2 mm, 41.5 ± 0.7 mm, 43.7 ± 0.8 mm, respectively; the corresponding changed angles of the spinal cord buckling were 62.8 ± 6.9°, 82.8 ± 7.5°, and 98.5 ± 7.0°. Significant differences of ΔH and Δα were found among the three groups by LSD multiple comparison test (P < 0.05). Strong correlation between ΔH and Δα was shown in each group by Pearson's correlation test. CONCLUSIONS: Different laminectomy extensions after 3-column osteotomy have different effects on the prevention of SCI caused by acute spinal shortening. The enlarged resection of lower lamina is superior to equidistant enlarged resection of upper and lower laminas which is superior to enlarged resection of upper lamina in preventing SCI. These slides can be retrieved under Electronic Supplementary Material.

[Advances in prostate-specific membrane antigen-mediated antitumor drugs].

Prostate cancer is the most prevalent male malignancy in the United States, and remains the second leading cause of cancer-related death in the male population. Prostate specific membrane antigen(PSMA) is a type of II transmembrane glycoproteins that is over-expressed in prostate cancer cell. More importantly, its expression is increased with cancer progression. PSMA has been a major target for imaging and therapeutic applications in prostate cancer. PSMA, also known as N-acetylated α-linked acidic dipeptidase I and folate hydrolase, can catalyze the hydrolysis of α- or γ-linked glutamates from peptides or small molecules. This article provides a review of the recent applications of ligand-drug conjugates targeting PSMA and prodrugs activated by PSMA.

Influence of vertebral column distraction on spinal cord volume: an experimental study in a goat model.

INTRODUCTION: Spinal cord injury may be related to excessive distraction of the spinal cord during surgical correction of spinal deformities by vertebral column resection. This study aimed to investigate how vertebral column distraction influences spinal cord volume to establish the safe range in a goat model. MATERIALS AND METHODS: A vertebral column resection was performed on the tenth thoracic vertebra of 11 goats. The spinal cord was distracted until the somatosensory evoked potential signals were decreased to 50 % from baseline amplitude or were delayed by 10 % of the baseline peak latency. The osteotomy segment was stabilized with a PEEK mesh cage filled with bone graft, and the pedicle screws on the rods were then tightened in this position. Spinal cord volume was calculated using Mimics software, and T10 height, disk height, osteotomy segment height, and spinal segment height were measured using the MRI image workstation. RESULTS: Three goats were excluded, and data obtained from the eight remaining goats were analyzed. The safe limit of distraction distance was 11.8 ± 3.65 mm, and the distraction distance was strongly correlated with the difference between the pre- and postoperative measurements (d value) of spinal cord volume per 1 mm of osteotomy segment height (r = -0.952, p < 0.001), but was not correlated with T10 body height (r = 0.16, p = 0.71), spinal segment height (r = 0.29, p = 0.49), disk height (r = -0.12, p = 0.98), or the d value (pre-post) of spinal cord volume per 1 mm of spinal segment height (r = 0.45, p = 0.26). The mean d value (pre-post) of spinal cord volume per 1 mm of osteotomy segment height was 10.05 ± 0.02 mm(3) (range 10.02-10.08 mm(3)). CONCLUSION: The maximum change in spinal cord volume per 1-mm change in height was in the osteotomy segment, and its safe limit was 10.05 ± 0.02 mm(3). The safe limit of spinal cord distraction can be calculated using the spinal cord volume per unit 1-mm change in height.

Enhancement of the synthesis of n-3 PUFAs in fat-1 transgenic mice inhibits mTORC1 signalling and delays surgically induced osteoarthritis in comparison with wild-type mice.

BACKGROUND: An exogenous supplement of n-3 polyunsaturated fatty acids (PUFAs) has been reported to prevent osteoarthritis (OA) through undefined mechanisms. OBJECTIVE: This study investigated the effect of alterations in the composition of endogenous PUFAs on OA, and associations of PUFAs with mammalian target of rapamycin complex 1 (mTORC1) signalling, a critical autophagy pathway in fat-1 transgenic (TG) mice. METHODS: fat-1 TG and wild-type mice were used to create an OA model by resecting the medial meniscus. The composition of the endogenous PUFAs in mouse tissues was analysed by gas chromatography, and the incidence of OA was evaluated by micro-computed tomography (micro-CT), scanning electron microscopy and histological methods. Additionally, primary chondrocytes were isolated and cultured. The effect of exogenous and endogenous PUFAs on mTORC1 activity and autophagy in chondrocytes was assessed. RESULTS: The composition of endogenous PUFAs of TG mice was optimised both by increased n-3 PUFAs and decreased n-6 PUFAs, which significantly alleviated the articular cartilage destruction and osteophytosis in the OA model (p<0.01), decreased protein expression of matrix metalloproteinase-13 (MMP-13) and ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin motifs) in the articular cartilage (p<0.01) and reduced chondrocyte number and loss of cartilage extracellular matrix. Both exogenous and endogenous n-3 PUFAs downregulated mTORC1 activity and promoted autophagy in articular chondrocytes. Conversely, mTORC1 pathway activation suppressed autophagy in articular chondrocytes. CONCLUSIONS: Enhancement of the synthesis of endogenous n-3 PUFAs from n-6 PUFAs can delay the incidence of OA, probably through inhibition of mTORC1, promotion of autophagy and cell survival in cartilage chondrocytes. Future investigation into the role of the endogenous n-6/n-3 PUFAs composition in OA prevention and treatment is warranted.

Clinical application of computer-aided design-rapid prototyping in C1-C2 operation techniques for complex atlantoaxial instability.

STUDY DESIGN: This is a retrospective clinical study. OBJECTIVE: To evaluate the clinical efficacy of computer-aided design-rapid prototyping (CAD-RP) techniques in surgical treatments for atlantoaxial instability (AAI). SUMMARY OF BACKGROUND DATA: The complexity of the upper cervical anatomic structures makes the procedures for the treatment of AAI particularly challenging for surgeons. The present study represents a series of C1-C2 surgery for AAI aided by CAD-RP. METHODS: A total of 49 patients (21 men and 28 women) with AAI were treated in our department. According to the use of the CAD-RP technique, the patients were divided into RP group and No RP group. Preoperative CT scans of the upper cervical spine were performed for each patient. For the RP group, physical RP models of the upper cervical spine were manufactured from the 3-dimensional CT data and were used for intraoperative guidance. Personalized surgeries were performed for each case of the 2 groups. The screw malposition rate, frequency of using intraoperative fluoroscopy, operation time, blood loss, and improvement of neurological function were compared between the 2 groups. The mean follow-up duration was 32 months (range, 24-50 mo). RESULTS: The operations were successfully performed in 48 cases expect for 1 case in the No RP group. A total of 204 screws were placed. The intraoperative fluoroscopy frequency and operation time were significantly lower in the RP group than that in the No RP group in both posterior and anterior approaches, whereas the screw malposition rate showed no difference between the 2 groups for both approaches. After the operation, 48 cases achieved satisfactory decompression of the cervical cord and repositioning of the atlantoaxial spine. During follow-up, 47 cases presented improvements in the spinal nerve function within 2 years. CONCLUSIONS: CAD-RP techniques have significant benefits for surgeons providing personalized treatments for AAI, especially cases with complicated deformities.

Effects of Planarization of the Triphenylamine Unit on the Electronic and Transport Properties of Triarylamine-Fluorene Copolymers in Both Doped and Undoped Forms.

Triarylamine-alt-fluorene (TAF) copolymers are widely used for hole injection and transport in organic electronics. Despite suggestions to planarize the triphenylamine moiety, little research has been conducted. Here, we report a comprehensive investigation of the effects of planarization on the electronic and transport properties of a model TAF polymer semiconductor core. We compared the conventional twisted-propeller N-4-methoxyphenyl-N,N-diphenylamine-4',4″-diyl (TA) unit and its planarized bridged analogue (bTA) where adjacent o,o'-positions are linked by 1,1-dimethylmethylene. We studied both polyelectrolyte and non-polyelectrolyte forms of this core in both doped and undoped states. We found that planarization leads to an unprecedented trap-free transport of holes, and a pronounced enhancement of their mobility in the undoped state though less so in the doped state. Planarization also induces a slight reduction in the ionization energy of the undoped polymer, consequently lowering the work function of the doped polymer. This is accompanied by small spectral shifts: a red shift in the first absorption band of the undoped polymer and a blue shift in the first absorption band of the polaron. Furthermore, this study unveils new fundamental features of TAF polymers: (i) Doping induces the formation of three polaron bands within the subgap. (ii) Absorption of both neutral and polaron segments exhibit a linear intensity relationship with doping level. (iii) Electrical conductivity reaches a maximum at the half-doped state, varying as σ ∼ (x (1 - x))3 for 0.1 ≲ x ≲ 0.9, where x is the doping level. Finally, we demonstrate the successful integration of these self-compensated hole-doped TAF polymers as efficient hole injection layers in organic semiconductor diodes.

Bindarit Reduces Bone Loss in Ovariectomized Mice by Inhibiting CCL2 and CCL7 Expression via the NF-κB Signaling Pathway.

OBJECTIVE: To investigate the changes in proinflammatory cytokines and chemokines, namely, C-C motif ligand (CCL) 2 and CCL7, in postmenopausal osteoporosis (PMOP) and to develop a new drug, bindarit (Bnd), for PMOP in an ovariectomized (OVX) mouse model. METHODS: Bone marrow macrophages (BMMs) from the femurs of five women with PMOP and five premenopausal women without osteoporosis were detected by RNA sequencing. BMMs from mice were differentiated into osteoclasts and treated with a synthetic inhibitor of CCL2 and CCL7, Bnd, or 17 beta estradiol (E2 ). Mouse BMMs were differentiated into osteoclasts with or without Bnd for 7 days and analyzed by RNA sequencing. Osteoblasts of mice were induced to undergo osteoblastogenesis and treated with Bnd. OVX mice were treated with E2 or Bnd after surgery. The protein and mRNA expression of CCL2 and CCL7 was detected using immunostaining and qPCR, respectively, in OVX and aged mice and in cells cultured in vitro. Osteoclast formation was detected using a tartrate-resistant acid phosphatase (TRAP) assay in vitro and in vivo. Alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) were detected using immunostaining to evaluate osteogenesis. Microcomputed tomography was conducted to analyze trabecular bone parameters, the structure model index, bone mineral density and other variables. Nuclear factor-κB (NF-κB) signaling pathway-related protein phosphorylation of IKKα/ß (p-IKKα/ß) and p-NFκB p65 was examined using western blotting. RESULTS: CCL2, CCL7 and their receptor of C-C chemokine receptor-2 (CCR2), and the NF-κB signaling pathway, were significantly increased in women with PMOP. CCL2 and CCL7 protein and mRNA expression was increased in OVX mice and aged female mice, but the increases were attenuated by E2 and Bnd. E2 and Bnd effectively inhibited osteoclastogenesis and the protein expression of CCL2 and CCL7 both in vitro and in vivo and reduced bone loss in OVX mice. Bnd did not affect the mineralization of osteoblasts directly in vitro but reduced bone turnover in vivo. p-IKKα/ß and p-NFκB p65 levels were increased in BMMs of mice after differentiation into osteoclasts but were significantly decreased by Bnd. CONCLUSION: The proinflammatory cytokines and chemokines CCL2, CCL7 and CCR2 were correlated with PMOP. Bnd attenuated the increases in CCL2 and CCL7 levels to affect osteoporosis in OVX mice via the NFκB signaling pathway. Thus, Bnd may be useful as a new therapeutic for the prevention of PMOP.

Personalised modified osteotomy using computer-aided design-rapid prototyping to correct thoracic deformities.

The correction of severe thoracic deformities is challenging. However, the usual imaging modalities are not sufficient for performing the surgery. Our objective was to describe the procedure and results of posterior modified wedge osteotomy aided by the techniques of computer-aided design-rapid prototyping (CAD-RP) to correct thoracic deformities. Twenty-one patients with thoracic deformities (eight males; 13 females) formed the study group. All patients underwent computed tomography (CT) scanning and CAD-RP, and a model of thoracic deformities and navigation templates of pedicles were created for each patient and used to analyse the spinal deformities and serve as anatomical reference. Aided by these models, personalised modified wedge osteotomy combining the eggshell technique and posterior vertebral column resection was performed. Using CAD-RP improved the safety and accuracy of surgery and screw placement in the 21 patients in whom 41 vertebrae were removed and 216 pedicle screws were placed. The average operation time was 260 (200-420) min, with an average blood loss of 1,900 ml (range 800-3560 ml). The percentage of deformity correction was 56.3% (from 72.1° to 31.5°) in the coronal plane and 60.4% (from 81.6° to 32.3°) in the sagittal plane. No patient had serious complications or implant failure. Personalised single-stage posterior modified wedge osteotomy is an effective procedure for treating thoracic deformities. Using CAD-RP and the RP models have significant benefits for personalised surgical treatment of complex thoracic deformities.

1-(4-Hydr-oxy-3,5-dimethoxy-phen-yl)ethanone.

In the title mol-ecule, C(10)H(12)O(4), the non-H atoms are essentially coplanar (r.m.s. deviation = 0.033 Å). In the crystal, mol-ecules are linked into chains along [001] by O-H⋯O hydrogen bonds.

5-(4-Bromo-anilinomethyl-ene)-2,2-dimethyl-1,3-dioxane-4,6-dione.

In the title compound, C(13)H(12)BrNO(4), the dihedral angles between the amino-methyl-ene group and the dioxane ring and between the benzyl ring and the amino-methyl-ene unit are 7.96 (4) and 12.15 (4)°, respectively. The dioxane ring shows a half-boat conformation, in which the C atom between the dioxane ring O atoms is 0.460 (8) Šout of the plane through the remaining ring atoms. An intra-molecular N-H⋯O hydrogen bond may stabilize the planar conformation of the mol-ecule. An inter-molecular C-H⋯O inter-action is also present.

5-(4-Chloro-anilinomethyl-ene)-2,2-dimethyl-1,3-dioxane-4,6-dione.

The title compound, C(13)H(12)ClNO(4), is approximately planar, with a dihedral angle of 8.23 (4)° between the mean plane of the amino-methyl-ene unit and the planar part of the dioxane ring. The dioxane ring has a half-boat conformation, in which the C atom between the dioxane O atoms is -0.464 (8) Šout of the plane of the other five atoms. In the mol-ecule there is an intra-molecular N-H⋯O hydrogen bond, involving the NH H atom and the adjacent dioxane carbonyl O atom. In the crystal, weak intermolecular C-H⋯O hydrogen-bonding contacts, result in the formation of sheets parallel to the ab plane.

Relationship between Spinal Cord Volume and Spinal Cord Injury due to Spinal Shortening.

Vertebral column resection is associated with a risk of spinal cord injury. In the present study, using a goat model, we aimed to investigate the relationship between changes in spinal cord volume and spinal cord injury due to spinal shortening, and to quantify the spinal cord volume per 1-mm height in order to clarify a safe limit for shortening. Vertebral column resection was performed at T10 in 10 goats. The spinal cord was shortened until the somatosensory-evoked potential was decreased by 50% from the baseline amplitude or delayed by 10% relative to the baseline peak latency. A wake-up test was performed, and the goats were observed for two days postoperatively. Magnetic resonance imaging was used to measure the spinal cord volume, T10 height, disc height, osteotomy segment height, and spinal segment height pre- and postoperatively. Two of the 10 goats were excluded, and hence, only data from eight goats were analyzed. The somatosensory-evoked potential of these eight goats demonstrated meaningful changes. With regard to neurologic function, five and three goats were classified as Tarlov grades 5 and 4 at two days postoperatively. The mean shortening distance was 23.6 ± 1.51 mm, which correlated with the d-value (post-pre) of the spinal cord volume per 1-mm height of the osteotomy segment (r = 0.95, p < 0.001) and with the height of the T10 body (r = 0.79, p = 0.02). The mean d-value (post-pre) of the spinal cord volume per 1-mm height of the osteotomy segment was 142.87 ± 0.59 mm3 (range, 142.19-143.67 mm3). The limit for shortening was approximately 106% of the vertebral height. The mean volumes of the osteotomy and spinal segments did not significantly change after surgery (t = 0.310, p = 0.765 and t = 1.241, p = 0.255, respectively). Thus, our results indicate that the safe limit for shortening can be calculated using the change in spinal cord volume per 1-mm height.

Glycemic Variation in Tumor Patients with Total Parenteral Nutrition.

BACKGROUND: Hyperglycemia is associated with poor clinical outcomes and mortality in several patients. However, studies evaluating hyperglycemia variation in tumor patients receiving total parenteral nutrition (TPN) are scarce. The aim of this study was to assess the relationship between glycemia and tumor kinds with TPN by monitoring glycemic variation in tumor patients. METHODS: This retrospective clinical trial selected 312 patients with various cancer types, whose unique nutrition treatment was TPN during the monitoring period. All patients had blood glucose (BG) values assessed at least six times daily during the TPN infusion. The glycemic variation before and after TPN was set as the indicator to evaluate the factors influencing BG. RESULTS: The clinical trial lasted 7.5 ± 3.0 days adjusted for age, gender, family cancer history and blood types. There were six cancer types: Hepatic carcinoma (HC, 21.8%), rectal carcinoma (17.3%), colon carcinoma (CC, 14.7%), gastric carcinoma (29.8%), pancreatic carcinoma (11.5%), and duodenal carcinoma (DC, 4.8%). The patients were divided into diabetes and nondiabetes groups. No statistical differences in TPN glucose content between diabetes and nondiabetes groups were found; however, the tumor types affected by BG values were obvious. With increasing BG values, DC, HC and CC were more represented than other tumor types in this sequence in diabetic individuals, as well as in the nondiabetic group. BG was inclined to be more easily influenced in the nondiabetes group. Other factors did not impact BG values, including gender, body mass index, and TPN infusion duration time. CONCLUSIONS: When tumor patients are treated with TPN, BG levels should be monitored according to different types of tumors, besides differentiating diabetes or nondiabetes patients. Special BG control is needed for DC, HC and CC in both diabetic and nondiabetic patients. If BG overtly increases, positive measurements are needed to control BG values. The ClinicalTrials.gov ID is NCT02024321.

[Three-dimensional dynamic contrast-enhanced magnetic resonance angiography in liver transplantation].

OBJECTIVE: To investigate the clinical value of three-dimensional dynamic contrast-enhanced magnetic resonance (MR) angiography in the liver transplantation. METHODS: MR scanning was performed both before and after the operation in 9 patients elected for liver transplantation, and after three-dimensional reconstruction at a computer workstation, the three- dimensional images of the inferior vena cava, hepatic veins, portal vein and bile duct were obtained. RESULTS: The three- dimensional images could be rotated in space to show the size, shape, lining of the veins and anatomic relationships between each other. CONCLUSION: Three-dimensional dynamic contrast-enhanced MR angiography can be of value in liver transplantation.

[Impact of early-stage hepatic ischemia-reperfusion injury on other organs of rats].

OBJECTIVE: To investigate the influence of hepatic ischemia-reperfusion on other organs of rats during the early stage of injury. METHODS: Twenty-five healthy male SD rats were randomized equally into 5 groups according to the different time points in the course of hepatic vascular occlusion and reperfusion, namely pre-occlusion, the end of occlusion, and after 0.5, 2.0 and 6.0 h reperfusion, respectively. In each group the rats were killed to obtain samples at the specified time points. The contents of malondialdehyde (MDA) and superoxide dismutase (SOD) in the lung, kidney, pancreas and heart were measured in pre-occlusion and 6-hour reperfusion groups. The triphosphate (ATPase) activity in heart tissues, the contents of MDA and the activity of SOD in blood and the blood biochemistry were observed in different groups. RESULTS: The activity of SOD and ATPase were decreased (P<0.05) after the ischemia-reperfusion as compared with those before ischemia, but the contents of MDA, ALT, AST BUN, AMY and CK-MB increased significantly (P<0.05). CONCLUSION: Liver ischemia-reperfusion can induce injury to other organs at the early stage of reperfusion.

[Establishment of canine models of acute mesenteric ischamia].

OBJECTIVE: To establish a new canine model of acute mesenteric ischemia for imaging studies. METHODS: Ten Beagle dogs were divided into ischemic group (n=8) and control group (n=2). Via a 4F Cobra catheter, the absolute ethanol was selectively injected into the superior mesenteric artery (SMA) for embolization in the former group while the saline was injected in the latter. Imaging study and pathological examination were performed. RESULTS: Digital subtraction angiography (DSA) revealed that occlusion of some branches of the SMA was induced in the ischemic group while no changes occurred in the control group. The signs of acute mesenteric ischemia were confirmed by CT and pathological examination in the ischemic group whereas no abnormalities identified in the group. CONCLUSION: Canine models of acute mesenteric ischemia can be established by selective catheterization with absolute ethanol injection.

[Combined operations for patients with hepatic cancer complicated by portal hypertension].

OBJECTIVE: To study the feasibility and operative procedures of liver resection in combination with collateral devascularization for treating patients with hepatic cancer complicated by portal hypertension. METHODS: A retrospective analysis was conducted in 45 cases of hepatectomy for hepatic cancer in combination with portaazygous devascularization for portal hypertension from Jan. 1995 to Jan. 2002. RESULTS: Operative mortality was zero. The absolute survival rate in 1/2, 1, 2, 3, 4, 5, 6, and 7 years was 44/45(97.8%), 30/41(73.2%), 26/36 (72.2%), 13/27(48.1%), 10/19(52.6%), 5/13(38.5%), 1/7(14.3%), 0/2(0) respectively. During hospitalization, refractory ascites occurred in 1 case and hepatorenal syndrome in another. Upper gastrointestinal hemorrhage occurred in 2 cases during the follow-up period. In the 14 patients who died during the follow-up, 9 died of cancer recurrence, 4 of liver function failure, and 1 of upper gastrointestinal hemorrhage. CONCLUSION: Hepatectomy in combination with portaazygous devascularization for patients with liver cancer complicated by portal hypertension is safe and feasible.

Multiple organ injury at early stage of intestinal and hepatic ischemia-reperfusion in rats.

OBJECTIVE: To investigate the early-stage multiple organ injuries in rats subjected to intestinal and hepatic ischemia-reperfusion. METHODS: Seventy-five normal male Wistar rats were randomized equally into hepatic ischemia, intestinal ischemia and intestinal-hepatic ischemia groups. Before and at the end of occlusion (45 min), as well as at the time points of 0.5, 2.0 and 6.0 h during the reperfusion, respectively, 5 rats from each group were killed to obtain samples for determination of the contents of malondialdehyde (MDA), superoxide dismutase (SOD) in the blood, lung, kidney, pancreas and heart tissues, along with blood urea nitrogen (BUN), amylase (AMY), and creatine kinase MB (CK-MB). RESULTS: The activity of SOD was decreased (P<0.05) and MDA, BUN, AMY and CK-MB levels increased significantly (P<0.05) after ischemia-reperfusion as compared with those before ischemia. CONCLUSIONS: Intestinal and hepatic ischemia-reperfusion can induce injury of multiple organs at early stage. With the same duration of ischemia-reperfusion, intestinal ischemia may induce severer injury than hepatic ischemia.

[Application of ischemic preconditioning before hepatic vascular exclusion for resection of hepatocellular carcinoma].

OBJECTIVE: To assess the value of clinical application of ischemic preconditioning (IP) before hepatic vascular exclusion for resection of hepatocellular carcinoma (HCC) accompanied by cirrhosis and explore the possible mechanism underlying the protective effect of this maneuver. METHODS: Thirty-four consecutive patients with resectable HCC were randomized into IP group to receive IP with a 5-min ischemia followed by 5-min perfusion before hepatic vascular exclusion and the control group with simply hepatic vascular exclusion. The liver function, hepatic Fas mRNA expression, caspase-3 activity, apoptosis of the hepatocytes were compared between the two groups. RESULTS: In the IP group, the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels on postoperative day 1, 3 and 7 were all significantly higher than those of the control group (t=6.985, P<0.01). The total bilirubin levels were also higher in the former group on postoperative day 3 and 7 (t=3.447, P<0.05). The IP group had higher albumin levels on postoperative day 1 than the control group (t=3.360, P<0.05). After 1 hour's reperfusion, the hepatic mRNA expression of Fas, caspase-3 activity and apoptotic sinusoidal endothelial cells were all significantly higher than those of the control group (t=3.771, P<0.05). CONCLUSION: IP has a protective effect on liver function after hepatic resection with hepatic vascular exclusion in HCC patients, possibly due to the inhibition of hepatocyte apoptosis by down-regulating hepatic Fas mRNA expression and caspase-3 activity, and is a convenient technique applicable in such operations as hepatic transplants and hepatectomy.

γ-secretase inhibitor-I enhances radiosensitivity of glioblastoma cell lines by depleting CD133+ tumor cells.

BACKGROUND AND AIMS: Glioblastoma is a deadly primary brain tumor with great resistance to radiotherapy. To reverse its radioresistance is important for improving prognosis. Gamma-secretase inhibitors (GSI) have been proven to have anti-tumor effects, yet the knowledge of their influences on glioblastomas is still limited. METHODS: The cytotoxic effects of GSI-I (a tripeptide GSI) on glioblastoma cell lines U87 and U251 were assessed by MTT assay, and the low concentration that did not induce significant cell death was determined. The in vitro radiosensitization effects of this low concentration of GSI-I were evaluated by cell colony forming assays. The CD133+ cell fractions before and after radiation with or without treatment of GSI-I were analyzed by flow cytometry. Then CD133+ and CD133- glioblastoma cells were sorted by magnetic activated cell sorting (MACS), and the radiosensitization effects of GSI-I on the two cell subtypes were investigated separately. Finally, the cytotoxic effects of GSI-I on CD133+and CD133- glioblastoma cells were examined, respectively, and the expression of the Notch pathway components between the two cell subtypes were compared. In addition, the anti-tumor effects of GSI-I were confirmed by in vivo experiments. RESULTS: GSI-I at a low concentration sensitized U87 and U251 cells to radiation by depletion of radioresistant CD133+ cells. CD133+ U87/U251 cells displayed preferential sensitivity to low concentrations of GSI-I, which may be related to the higher expression of the Notch signaling pathway in these cells. CONCLUSIONS: Combining GSI-I with radiotherapy may represent a promising strategy for treating radioresistant gliomas.