Search

Tweety-homolog 1 (Ttyh1) is expressed in neural tissue and has been implicated in the generation of several brain diseases. However, its functional significance in pain processing is not understood. By disrupting the gene encoding Ttyh1, we found a loss of Ttyh1 in nociceptors and their central terminals in Ttyh1-deficient mice, along with a reduction in nociceptor excitability and synaptic transmission at identified synapses between nociceptors and spinal neurons projecting to the periaqueductal grey (PAG) in the basal state. More importantly, the peripheral inflammation-evoked nociceptor hyperexcitability and spinal synaptic potentiation recorded in spinal-PAG projection neurons were compromised in Ttyh1-deficient mice. Analysis of the paired-pulse ratio and miniature excitatory postsynaptic currents indicated a role of presynaptic Ttyh1 from spinal nociceptor terminals in the regulation of neurotransmitter release. Interfering with Ttyh1 specifically in nociceptors produces a comparable pain relief. Thus, in this study we demonstrated that Ttyh1 is a critical determinant of acute nociception and pain sensitization caused by peripheral inflammation. [ABSTRACT FROM AUTHOR]

Nuclear localization of PTEN is essential for its tumor suppressive role, and loss of nuclear PTEN is more prominent than cytoplasmic PTEN in many kinds of cancers. However, nuclear PTEN-specific regulatory mechanisms were rarely reported. Based on the finding that nuclear PTEN is more unstable than cytoplasmic PTEN, here we identify that F-box only protein 22 (FBXO22) induces ubiquitylation of nuclear but not cytoplasmic PTEN at lysine 221, which is responsible for the degradation of nuclear PTEN. FBXO22 plays a tumor-promoting role by ubiquitylating and degrading nuclear PTEN. In accordance, FBXO22 is overexpressed in various cancer types, and contributes to nuclear PTEN downregulation in colorectal cancer tissues. Cumulatively, our study reports the mechanism to specifically regulate the stability of nuclear PTEN, which would provide the opportunity for developing therapeutic strategies aiming to achieve complete reactivation of PTEN as a tumor suppressor. Loss of nuclear PTEN is associated with aggressive cancers. Here the authors show that nuclear PTEN is more susceptible to ubiquitin-mediated proteasomal degradation than cytoplasmic PTEN, and identify FBXO22 ubiquitinates and degrades nuclear PTEN to promote tumorigenesis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the safety and feasibility of totally laparoscopic uncut Roux-en-Y anastomosis in the distal gastrectomy with D2 dissection for gastric cancer. We also summarized the preliminary experience of totally laparoscopic uncut Roux-en-Y anastomosis.Methods: A retrospective analysis was done in 51 cases of total laparoscopic uncut Roux-en-Y anastomosis in the distant gastrectomy with D2 dissection for gastric cancer in our hospital from September 2014 to December 2015.Results: All of 51 cases underwent total laparoscopic uncut Roux-en-Y anastomosis. All the procedures were performed successfully. There were neither conversions to open surgery nor intraoperative complications in all 51 cases. In this study, the median operative time was 170 (135-210) min and the median time of anastomosis was 27 (24-41) min. The blood loss was 60 (30-110) ml. The time to flatus and length of postoperative hospital stay were 2 (1-3) days, and 8 (7-12) days, respectively. The mean lymph node harvest was 34 (18-49). One anastomotic bleeding occurred postoperatively which was cured by conservative treatment. No major postoperative complication occurred, such as anastomotic leak, anastomotic stenosis, and Roux stasis syndrome. After a short-term follow-up, no recanalization or reflux gastritis was encountered by endoscopy.Conclusion: The totally laparoscopic uncut Roux-en-Y anastomosis in distal gastrectomy with lymph node dissection for gastric cancer is safe and feasible, with a very low rate of recanalization and reflux gastritis. [ABSTRACT FROM AUTHOR]

The outcome of spinal cord injury (SCI) is determined by both neural cell-intrinsic survival pathways and tissue microenvironment-derived signals. Macrophages dominating the inflammatory responses in SCI possess both destructive and reparative potentials, according to their activation status. Notch signaling is involved in both cell survival and macrophage-mediated inflammation, but a comprehensive role of Notch signaling in SCI has been elusive. In this study, we compared the effects of general Notch blockade by a pharmaceutical γ-secretase inhibitor (GSI) and myeloid-specific Notch signal disruption by recombination signal binding protein Jκ (RBP-J) knockout on SCI. The administration of Notch signal inhibitor GSI resulted in worsened hind limb locomotion and exacerbated inflammation. However, mice lacking RBP-J, the critical transcription factor mediating signals from all four mammalian Notch receptors, in myeloid lineage displayed promoted functional recovery, attenuated glial scar formation, improved neuronal survival and axon regrowth, and mitigated inflammatory response after SCI. These benefits were accompanied by enhanced AKT activation in the lesion area after SCI. These findings demonstrate that abrogating Notch signal in myeloid cells ameliorates inflammation response post-SCI and promotes functional recovery, but general pharmaceutical Notch interception has opposite effects. Therefore, clinical intervention of Notch signaling in SCI needs to pinpoint myeloid lineage to avoid the counteractive effects of global inhibition. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the applicability, safety, short-term and long-term outcomes of laparoscopic surgery in the treatment of right-sided colon carcinomas with D3 lymphadenectomy. Methods: Between June 2003 and September 2010, 324 patients with right-sided colon carcinoma underwent surgical treatment in the same hospital, 177 cases were treated by laparoscopic surgery (LRH group) and 147 cases by open surgery (ORH group). We performed a retrospective analysis of the differences between the two groups in terms of the clinical data. Results: There were no significant differences between the two groups in the demographic data; however, the recovery time was significantly shorter in the LRH group, the number of overall lymph nodes harvested and principle lymph nodes harvested in the LRH group was significantly higher than in the ORH group, the incidence of postoperative complications was 12.99 % in the LRH group and 22.45 % in the ORH group ( P < 0.05), and the recurrence rate in the LRH group was lower than that in the ORH group, although the difference was not significant (15.25 vs 19.73 %). The cumulative overall survival for all stages at 1, 3 and 5 years in the LRH group (97.18, 83.73 and 70.37 %) were not significantly different compared to those in the ORH group (94.56, 77.84 and 66.97 %). Conclusions: Laparoscopic-assisted right hemicolectomy with D3 lymphadenectomy for colon carcinomas is safe and effective, while it is also superior to open surgery regarding the short-term outcomes, and the long-term outcomes are similar to those of open surgery. [ABSTRACT FROM AUTHOR]

Objective: To explore the feasibilities between operational approaches for laparoscopic complete mesocolic excision (CME) to right hemicolon cancer. Methods: This prospective randomized controlled trial included patients admitted to a Shanghai minimally invasive surgical center to receive laparoscopic CME from September 2011 to January 2013 randomized into two groups: hybrid medial approach (HMA) and completely medial approach (CMA). The feasibilities and strategies of the two techniques were studied and compared. Furthermore, the operation time and vessel-related complications were designed to be the primary end points, and other operational findings, including the classification of the surgical plane and postoperative recovery, were designed to be the secondary end points for this study. Results: After screening, 50 cases were allocated to the HMA group and 49 to the CMA group. Within the HMA group, there were 48 cases graded with mesocolic plane and 2 with intramesocolic plane. For the CMA group, there were 42 cases graded with mesocolic plane and seven with intramesocolic plane. The differences between the two were insignificant, as were the number of lymph nodes retrieved. The mean±standard deviation total operation time for the CMA group was 128.3 ± 36.4 min, which was significantly shorter than that for the HMA group, 142.6 ± 34.8 min. For the CMA group, the time involved in central vessel ligations and laparoscopic procedures was 58.5 %, 14.1 and 81.2 ± 23.5 min, respectively, which were shorter than the HMA group. The vessel-related complication rate was significantly higher in the HMA group. Conclusions: Laparoscopic CME via the total medial approach is technically feasible after the precise identification of the surgical planes and spaces for the right hemicolon. The procedure has a shorter operation time and fewer vessel-related complications. [ABSTRACT FROM AUTHOR]

Purposes: To study the feasibility, safety, and short-/long-term outcomes of laparoscopy-assisted right hemicolectomy with D3 lymphadenectomy for colon cancer. Methods: The clinical data of 177 cases that underwent laparoscopy-assisted radical right hemicolectomy with D3 lymphadenectomy for colon cancer between Jun 2003 and Sep 2010 was collected; the safety of operation, status of recovery, complication, oncological outcomes, and results of short-/long-term follow-up were analyzed. Results: No case died in this study; five cases (2.82 %) were converted to open surgery. Four cases (2.26 %) underwent hand-assisted laparoscopic right hemicolectomy. The average operation time was 133 ± 36 min, and the blood loss was 94 ± 34 ml. The average time for passage of flatus, liquid food eating, and hospitalization were 2.1 ± 0.7, 3.2 ± 0.5, and 10.4 ± 2.7 day, respectively. The total number of lymph nodes removed was 15.2 ± 10.1. Postoperative complications were observed in 23 of 177 patients (12.99 %). The median follow-up period was 54 months; port-site recurrence was observed in one patient; local recurrence was found in five cases (2.82 %); distant metastasis was found in 21 cases (11.86 %). The cumulative overall survival of all stages at 12, 36, 60, and 72 months was 97.18 %, 83.73 %, 70.37 %, and 68.99 %, respectively. The cancer-specific survival was 98.73 % (12 months), 87.81 % (36 months), and 80.17 % (60 months). Conclusions: Laparoscopy-assisted right hemicolectomy with D3 lymphadenectomy can be successfully performed for right colon cancer with the advantages of minimally invasive surgery. Moreover, the results implied appropriate short- and long-term outcomes. [ABSTRACT FROM AUTHOR]

Objective: This study was designed to investigate the feasibility and technical strategies of laparoscopic complete mesocolic excision (CME) for right-hemi colon cancer. Methods: The clinical and pathological findings of 64 patients with right-hemi colon cancer who underwent laparoscopic CME between March 2010 and September 2011 were collected retrospectively. Among them, 35 cases were eligible for the final analysis through various screening factors. The quality of surgery also was assessed by reviewing the recorded video obtained through the operations in terms of specimen anatomic planes and completeness of the excised mesocolon. Results: Laparoscopic CME is focused on applying the concept of enveloped visceral and parietal planes during the operations. Laparoscopic approach proceeds with medial access where the dissection starts at ileocolic vessel before proceeds along with the superior mesenteric vessel. The access also emphasized en bloc resection of mesocolon without defections to the planes. Besides, lymph node resections at the root of ileocolic; right colic and middle colic vessels are necessary for ileocecum cancer. Cancers at the hepatic flexure requires further dissection of subpyloric lymph nodes and of greater omentum that is within 15 cm of the tumor and along the greater curvature. Thirty-five cases were evaluated as good plane. The median total number of central lymph nodes retrieved was 19 (range, 15-25) and central lymph node metastasis was found in 5 of all stage III cases. The median operation time was 2.6 h and the blood loss was 80 mL. The median time for passage of flatus and hospitalization were 2 and 12 days respectively. Complications were observed in three cases. Conclusions: CME is a novel concept for colon cancer surgery and might be a standard for the procedure. Laparoscopic CME with medial access is technically feasible and randomized trials are needed to evaluate its long-term outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Lateral lymph node metastasis is common in papillary thyroid microcarcinoma (PTMC). The present study evaluated the clinicopathologic characteristics and ultrasonographic (US) findings in predicting lateral LNM from PTMC in eastern China. Materials and methods: A total of 176 patients with confirmed PTMC by final histological examination who underwent central lymph node dissection (LND) and lateral LND were enrolled in our study. The clinicopathological and US data from the cases were analyzed retrospectively to determine the independent predictive factors for lateral LNM. Then, a scoring system was developed on the basis of independent factors. The sum of the points for individuals was evaluated for the value in predicting lateral LNM. Results: Central LNM, underlying Hashimoto's thyroiditis, upper pole location, no well-defined margin and presence of calcifications were independent predictive factors for lateral LNM on multivariate analysis. Clinicopathological and US index points were statistically significant, with ≤2 favoring lateral LNM negativity with a sensitivity of 83.3 %, positive predictive value of 89.6 % and negative predictive value of 72.9 %. Conclusions: When the evaluation for lateral lymph nodes from a preoperative approach is inadequate or not obvious, our scoring system for prediction of lateral LNM can be another choice. Patients with clinicopathological and US index points ≤2 could be considered as lateral LNM negative, so more diagnostic approach is recommended for patients with clinicopathological and US index points >2. [ABSTRACT FROM AUTHOR]

Background: Cancer stem-like cells (CSCs) in colorectal cancers (CRC) may account for the failure of treatments because they are resistant to many current anticancer therapies. Salinomycin, a potassium ionophore, was recently identified as a selective inhibitor of breast CSCs. Methods: The human CRC cell lines HT29 and SW480 were treated with salinomycin and oxaliplatin. Cell viability was determined with cell counting kit 8. Fraction of CD133+ cell subpopulations was assessed by Flow Cytometric analysis. Clonogenecity and migration were determined with soft agar and Boyden chamber assays. Molecular changes were assessed by immunofluorescence staining, RT-PCR, and Western blot analysis. Results: We report that salinomycin reduces the proportion of CD133+ subpopulations in human CRC HT29 and SW480 cells. Furthermore, salinomycin treatment decreases colony-forming ability and cell motility in HT29 cells. Moreover, salinomycin downregulates the expression of vimentin and induces the E-cadherin expression in HT29 cells. Conclusions: This study demonstrates the ability of salinomycin to selectively target 'CD133+' cell subpopulations and decrease the malignant traits in colorectal cancer lines. [ABSTRACT FROM AUTHOR]