Epigenetic regulation of papillary thyroid carcinoma by long non-coding RNAs.

Thyroid cancer is the most common primary endocrine malignancy with papillary thyroid carcinoma (PTC) its most common subtype. The jump in diagnoses over last many years has prompted re-assessment of molecularly targeted therapies and the discovery of novel targets. Long non-coding RNAs (lncRNAs) are increasingly being assessed for their expression in various PTC models. Interestingly, in addition to cell line models, a large proportion of the reported studies have evaluated lncRNA levels in PTC patient samples providing an immediate clinical relevance of their findings. While most lncRNAs either promote or suppress PTC pathogenesis, data on individual lncRNAs is not very clear. As expected, lncRNAs function in PTC through sponging of microRNAs as well as modulation of several signaling pathways. The process of epithelial-mesenchymal transition and the PI3K/Akt and wnt signaling pathways have emerged as the primary targets of lncRNAs in PTC. This comprehensive review discusses all the information that is available on lncRNAs in PTC, ranging from in vitro and in vivo findings to the possible role of lncRNAs as diagnostic and/or prognostic biomarkers.

Epigenetic signature associated with thyroid cancer progression and metastasis.

Thyroid cancer is not among the top cancers in terms of diagnosis or mortality but it still ranks fifth among the cancers diagnosed in women. Infact, women are more likely to be diagnosed with thyroid cancer than the males. The burden of thyroid cancer has dramatically increased in last two decades in China and, in the United States, it is the most diagnosed cancer in young adults under the age of twenty-nine. All these factors make it worthwhile to fully understand the pathogenesis of thyroid cancer. Towards this end, microRNAs (miRNAs) have constantly emerged as the non-coding RNAs of interest in various thyroid cancer subtypes on which there have been numerous investigations over the last decade and half. This comprehensive review takes a look at the current knowledge on the topic with cataloging of miRNAs known so far, particularly related to their utility as epigenetic signatures of thyroid cancer progression and metastasis. Such information could be of immense use for the eventual development of miRNAs as therapeutic targets or even therapeutic agents for thyroid cancer therapy.

LncRNA SNHG14 Sponges miR-206 to Affect Proliferation, Apoptosis, and Metastasis of Hepatocellular Carcinoma Cells by Regulating SOX9.

OBJECTIVE: To explore how lncRNA SNHG14 modulates the biological features of hepatocellular carcinoma (HCC) cells by regulating SOX9 via mediating miR-206. METHODS: HCC tissues were collected to perform the quantitative reverse transcriptase polymerase chain reaction to determine the expressions of SNHG14, miR-206, and SOX9. HCC cell line SMCC7721 was selected for co-transfection by si-SNHG14/miR-206 inhibitor/si-SOX9, followed by the measurement of cell proliferation using Cell Count Kit-8 (CCK-8) assay and clone formation assay. The migration and invasion were evaluated by wound healing test and Transwell assay. The apoptotic rate was determined by flow cytometry. Levels of the apoptosis-related proteins were measured through Western blotting. RESULTS: SNHG14 and SOX9 were up-regulated in HCC tumor tissues compared with adjacent normal tissues, with decreased miR-206 expression. Moreover, SNHG14 expression was significantly associated with the TNM stage, lymphatic metastasis, and histological differentiation of HCC patients. Besides, inverse correlations between SNHG14 and miR-206, as well as between miR-206 and SOX9, were noted. The dual luciferase reporter gene assay, RIP, and RNA pull-down experiments also revealed the targeting relationship between SNHG14 and miR-206 or between miR-206 and SOX9. Silencing SNHG14 and SOX9 inhibited the proliferation, invasion, and migration of HCC cells, with increased apoptosis, which was all abolished by silencing miR-206. CONCLUSION: Inhibition of SNHG14 suppresses SOX9 by up-regulating miR-206, to further inhibit the proliferation, migration, and invasion of HCC cells with the promoted apoptosis, which is a novel target for the treatment of HCC.

Mefloquine targets ß-catenin pathway and thus can play a role in the treatment of liver cancer.

The current study was designed and performed to investigate the effect of mefloquine on the proliferation and tumor formation potential of liver cancer stem cells. CD133 + HepG2 cells were identified using MACS and showed markedly higher tumor formation potential compared to the parental cells. The secondary tumors formed by CD133 + cells were markedly large in size and more in number compared to the parental cells. Mefloquine treatment of CD133 + HepG2 cells inhibited the proliferation selectively in concentration based manner. The rate of proliferation was inhibited to 82 and 12% in parental and CD133 + sphere forming cells, respectively on treatment with 10 µM concentration of mefloquine. The number of secondary tumors formed by primary tumors was decreased significantly on treatment with 10 µM mefloquine concentration. Treatment of the liver cancer stem cells with mefloquine markedly decreased the potential to undergo self-renewal at 10 µM concentration after 48 h. The results from western blot analysis showed significantly higher expression of cancer stem cell molecules ß-catenin and cyclin D1 in LCSCs. Treatment of the LCSCs with various concentrations of mefloquine reduced the expression levels of ß-catenin and cyclin D1. Administration of the CD133 + cell tumor xenografts in the mice led to the formation of large sized tumors in the control group. However, the tumor growth was inhibited significantly in the mice on treatment with 10 mg/kg doses of mefloquine after day 21. The tumor weight was significantly lower in the animals of mefloquine treatment group compared to the control group. Thus, mefloquine treatment inhibits self-renewal and proliferation potential of cells through targeting ß-catenin pathway.

Prognostic role of the peritoneal cancer index in ovarian cancer patients who undergo cytoreductive surgery: a meta-analysis.

Advanced-stage ovarian cancer is usually associated with peritoneal carcinomatosis. This study evaluates the prognostic role of the Peritoneal Cancer Index (PCI) in predicting the survival of patients with ovarian cancer. A literature search was conducted in electronic databases (Google Scholar, PubMed, Ovid, and Science Direct) and study selection was based on precise eligibility criteria. Random-effects meta-analyses were performed to estimate survival with low and high PCI scores and to pool hazard ratios (HR) of survival between lower and higher PCI scores. A total of 20 studies (2588 patients) were included. Median follow-up was 39 months [95%CI: 25, 54]. Complete cytoreduction rate was 80% [95% CI: 73, 87]. The median PCI score was 11.3 [95% CI: 9.9, 12.7]. Median survival was 56.7 months [95% CI: 45.2, 68.2] with below and 28.8 months [95% CI: 23.0, 34.6] with above any PCI cutoff. Most studies used PCI cutoffs between 10 and 20. The median progression-free survival was 23.7 months [95% CI: 16.5, 30.8] with below and 11.9 months [95% CI: 5.9, 17.9] with above any PCI cutoff. 5-year survival rates were 61.3% [95% CI: 49.9, 72.8] with PCI<10 cutoffs, 21.7% [95% CI: 11.6, 31.8] with PCI>10 cutoffs, 50.1% [95% CI: 39.0, 61.2] with PCI<20 cutoffs, and 21.7% [95% CI: 16.2, 27.1] with PCI>20 cutoffs. Pooled analysis of HRs showed that a higher PCI score was associated with worse survival in both univariate (HR 2.14 [95%CI: 1.63, 2.66]) and multivariate (HR 1.10 [95% CI: 1.02, 1.18]) analyses. In a set of studies that used varying PCI cutoffs, the PCI has been found to have a significant inverse association with the survival of patients with advanced ovarian cancer who underwent cytoreductive surgery.

Erratum: Role of ursolic acid chalcone, a synthetic analogue of ursolic acid, in inhibiting the properties of CD133(+) sphere-forming cells in liver stem cells.

[This corrects the article on p. 1427 in vol. 8, PMID: 25973027.].

Role of ursolic acid chalcone, a synthetic analogue of ursolic acid, in inhibiting the properties of CD133(+) sphere-forming cells in liver stem cells.

The expression of CD133 decreases with differentiation of tumor cell, indicating that CD133 is a specific marker for isolation and identification of CSCs. In the present study the effect of Ursolic acid chalcone (UAC) on CD133(+) hepatocellular carcinoma cell (HCC CSCs) differentiation, their self-renewal, tumorigenic capacity and sensitivity to chemotherapeutic drugs was studied. The results demonstrated that UAC inhibits the expression of CD133(+) in a dose and time-dependent manner in PLC/PRF/5 and Huh7 HCC cells. The inhibition was significant at 50 µM and on day 8. The percentage of CD133(+) cells decreased from an initial 59.3% in PLC/PRF/5 to 37.1% and 78.2% in Huh7 to 59.2% on treatment with UAC. There was inhibition of Oct4, Tert, Bmi1, ß-catenin, ABCG2, and tumor sphere-related gene Ep300. In addition it also decreased number of CK19-positive cells and increased number of CK8/18-positive cells. UAC treatment caused a decrease in self-renewal capability and increase in sensitivity to doxorubicin and vincristine drugs in CD133(+) HCC CSCs. Therefore, UAC can be a potent therapeutic agent to target differentiation of CSC in HCC.

hARIP2 is a putative growth-promoting factor involved in human colon tumorigenesis.

Activin is a multifunctional growth and differentiation factor of the growth factor-beta (TGF-ß) superfamily, which inhibits the proliferation of colon cancer cells. It induces phosphorylation of intracellular signaling molecules (Smads) by interacting with its type I and type II receptors. Previous studies showed that human activin receptor-interacting protein 2 (hARIP2) can reduce activin signaling by interacting with activin type II receptors; however, the activity of hARIP2 in colon cancer has yet to be detailed. In vitro, overexpression of hARIP2 reduced activin-induced transcriptional activity and enhanced cell proliferation and colony formation in human colon cancer HCT8 cells and SW620 cells. Also, hARIP2 promoted colon cancer cell apoptosis, suggesting that a vital role in the initial stage of colon carcinogenesis. In vivo, immunohistochemistry revealed that hARIP2 was expressed more frequently and much more intensely in malignant colon tissues than in controls. These results indicate that hARIP2 is involved in human colon tumorigenesis and could be a predictive maker for colon carcinoma aggressiveness.

[Three-dimensional finite element analysis on mechanical behavior of the bone remodeling and bone integration between the bone-implant interface after hip replacement].

OBJECTIVE: To discuss the primary stability of the fixed interface between the cementless prosthesis and femur, and its influence on bone ingrowth and secondary stability under the roughened surface and press fit of different prostheses by finite element analysis. METHODS: :A three-dimensional finite element module of total hip arthroplasty (THA) was developed with Mimics software. There was a collection of data when simulating hip arthroplasty. The frictional coefficient between the fixed interface was 0,0.15,0.40 and 1.00 representing the roughness of prosthesis surface. The press fit was 0, 0.01,0.05 and 0.10 mm according to the operation. The Vion Mises stress distribution and the contact pressure,friction stress and relative sliding displacement between the interface were analysed and compared when simulating the maneuver of climbing stairs. RESULTS: At a fixed press fit of 0.05 mm,the contact pressure between the interface was 230 , 231, 222 and 275 MN under four different frictional coefficient (0,0. 15,0.40 and 1.00) with little change; the relative sliding displacement was 0.529, 0.129, 0.107 and 0.087 mm with a consistent and obvious decline. As the fixed frictional coefficient was 0.40,the contact pressure between the interface were 56.0,67.7 ,60.4 and 49.6 MN under four different press fit (0, 0.01, 0.05 and 0.10 mm) with a reduction; the relative sliding displacement was 0.064,0.062,0.043 and 0.042 mm with an obvious decline, and there was a maximal friction stress when press fit of 0.01 mm. CONCLUSION: There is a dynamic process of the bone remodeling and bone integration between the interface after hip replacement, determining the long-term outcome. The interface clearance and the frictional coefficient are the key factors of the bone integration.

[Clinical apprehension on application of Tri-lock BPS total hip arthroplasty].

OBJECTIVE: To study short-term results and clinical application of Tri-lock BPS in total hip arthoplasty. METHODS: From May 2010 to July 2011, 32 hips in 31 patients (18 males and 13 females, ranging in age from 50 to 77 years old, with an average of 60.5 years old) were treated by total hip arthroplasty with Tri-lock BPS, including 8 patients with osteonecrosis (ON), 13 patients with fresh femoral neck fracture, 10 patients with developmental dysplasia of the hip (DDH). The therapeutic effects were evaluated by self assessment form, preoperative and postoperative Harris hip score, radiographs, Engh score and bone in growth of femoral side described by Gruen. Based on the short-term results,its design characteristic and clinical properties were analyzed. RESULTS: All the incisions healed well and there were no complications such as femoral fracture, infection, dislocation and neurovascular injuries. All the patients were followed up with an average time of 12.2 months (ranged, 10 to 14 months). All the joints had good or excellent clinical results. The Harris score increased from preoperative 38.3 +/- 4.9 to 92.5 +/- 11.2 at the latest follow-up (t = 27.53, P < 0.01). Radiographically, the positions of the prostheses were normal,the average limbs length and femoral eccentricity recovered to normal. X-ray of the hips showed that the femoral stem prosthesis was in line with good initial fixed standard. At 3 months after surgery, X-ray of the hips showed that bone in growth in Gruen II and VI of femoral side. CONCLUSION: Short-term results show that the design of Tri-lock BPS is more in line with human anatomy, and has the advantages in rapid recovery of hip function and retains more bone mass. It offers a newly valuable technology for the treatment of osteonecrosis, femoral neck fracture and DDH and so on.

[Case-control study on combined therapy for preventing postsurgery stiffness after elbow fracture].

OBJECTIVE: To research the efficacy,security and necessity of combined therapy for preventing postsurgery stiffness after elbow fracture. METHODS: From May 2009 to April 2010, 60 patients with elbow fractures treated by operation were randomly divided into two groups: combined therapy group and past procedure group. Thirty patients in the combined therapy group,including 12 males and 18 females, ranging in age from 23 to 63 years, averaged (43.53 +/- 7.74) years old; 15 patients had two parts fractures, including humeral intercondylar fractures combined with olecroanon and (or) ulna coronoid process fractures in 8 cases, fractures of exterior and interior humeral condyle combined with capitulum radius in 3 cases, fractures of olecroanon and ulna coronoid process in 3 cases, fractures of olecroanon and capitulum radius in 1 case; other 15 patients had one part fractures, including fractures of exterior or interior humeral condyle in 8 cases,fractures of olecroanon or ulna coronoid process in 6 cases, fractures of capitulum radius in 1 patient. Thirty patients in the past procedure group,including 11 males and 19 females, ranging in age from 24 to 67 years, averaged (46.13 +/- 6.22) years; 15 patients had two parts fractures, including fractures of humeral intercondylar fracture combined with olecroanon and(or) ulna coronoid process in 7 cases, fractures of exterior and interior humeral condyle combined with capitulum radius in 2 cases,fractures of olecroanon and ulna coronoid process in 5 cases,fractures of humeral intercondylar fracture combined with capitulum radius in 1 patient; 15 pa- tients had one part fracture, including fractures of exterior or interior humeral condyle in 6 cases, fractures of olecroanon or ulna coronoid process in 8 cases, fractures of capitulum radius in 1 patient; the patients in the past procedure group were treated with past procedure methods. Mayo Elbow Performance Score (including gmotion of elbow joint) and security (using X-ray to recheck displacement fracture, internal fixation failure and heterotopic ossification) were evaluated at postoperative 6 months. From 2002 to 2006, 30 patients were reviewed as historical control group, including 17 males and 13 females, ranging in age from 27 to 62 years, averaged (47.17 +/- 7.83) years; 15 patients had two parts fractures, including fractures of humeral intercondylar combined with olecroanon and(or) ulna coronoid process in 7 cases, fractures of exterior and interior humeral condyle combined with capitulum radius in 1 case, fractures of olecroanon and ulna coronoid process in 6 cases, fractures of ulna coronoid process and capitulum radius in 1 case; 15 patients had one part fractures,including fractures of exterior or interior humeral condyle in 9 cases, fractures of olecroanon or ulna coronoid process in 5 cases,fractures of capitulum radius in 1 case. The Mayo Elbow Performance Score of the patients in historical control group was evaluated retrospectively at postoperative 6 months and the results were compared with that of past procedure group. RESULTS: Mayo score of combined therapy group was (91.00 +/- 7.81)surpassed to (76.83 +/- 10.71) of the past procedure group and (73.17 +/- 1.99) of historical control group (F = 24.98, P < 0.05). The range of motion of elbow was (102.40 +/- 9.16) degrees of combined therapy group surpassed to (83.57 +/- 6.21) degrees of the past procedure group (t = 9.325, P < 0.05). There were no internal fixation loose,obvious fracture displacement and heterotopic ossification in each X-ray examination of patients in the combined therapy group. The Mayo score of historical control group was (73.17 +/- 11.99), showing no significant differences when compared with (76.83 +/- 10.71) of the past procedure group (LSD, P = 0.172). CONCLUSION: Combined therapy including different stage, different method combination and different subject to practice to prevent postsurgery stiffness after elbow fracture is effect, security and necessity.

[Clinical study on second-stage revision in the postoperative infection after total hip replacement].

OBJECTIVE: To study the therapeutic effects and clinical experiences of second-stage revision in postoperative infection after total hip replacement and to explore its security and validity. METHODS: From January 2006 to March 2009, 17 hips in 17 patients (7 males and 10 females, ranging in age from 43 to 75 years, with an average of 58.5 years) were treated with second-stage revision. All the patients suffered from different degrees of hip pain. In bacilliculture of Synovial fluid or peritonsillar tissue, 11 patients showed positive results and 6 patient negative. The intraoperative periprosthetic histopathological examination showed that all the patients had acute inflammation. Eight patients had sinus communicating with prosthesis; 15 patients had increased ESR, and 15 patients had C reactive protein increased. All the patients had osteolysis, prosthesis loosening, and the performance of periosteal reaction in X-ray. All the patients were treated with second stage revision. In the first operation, thorough debridement was perfumed and the prosthesis was removed. Then the prosthesis of antibiotic--loaded acrylic cement was implanted. After giving antibiotics intravenously for 4 weeks, the antibiotics were taken orally for another six weeks. The ESR and C response protein were examined at regular time, and the second-stage revision surgery was perfumed when the ESR and C response protein were normal. The Harris score was used to evaluate therapeutic effects of second-stage revision surgery before and after treatment. RESULTS: All the patients were followed up with an average of 19.5 months, ranged from 12 to 35 months. No complications occurred. Postoperative X-ray showed prosthesis in the correct position. The Harris score increased from preoperative (39.3 +/- 5.6) to postoperative (84.4 +/- 10.3) (t = 15.86, P < 0.01). CONCLUSION: The second-stage revision in postoperative infection after total hip replacement has a good efficacy, safety and reliability advantages. This technology provides an alternative in postoperative infection after total hip replacement.

[Clinical apprehension on application of metal on metal total hip arthroplasty with large diameter heads].

OBJECTIVE: To approach the short-term result and clinical application of metal on metal total hip arthroplasty with large diameter heads and evaluate its safety and efficacy clinically. METHODS: From January 2007 to March 2008, 39 hips in 37 patients (24 males and 13 females,ranging in age from 43 to 75 years, with an average of 58.5 years) were treated with metal on metal total hip arthroplasty with large diameter heads (ASRTM XL) included 14 cases of osteonecrosis (ON), 2 cases of osteoarthritis (OA), 18 cases of fresh femoral neck fracture, 3 cases of developmental dysplasia of the hip (DDH). All patients were evaluated by self assessment form, hip function examination, radiographs, preoperative and postoperative Harris hip score. Based on the short-term results, its design characteristic and clinical properties were analyzed. RESULTS: All the incision healed well and there were not any complications such as femoral fracture, infection, dislocation and neurovascular injury. All patients obtained the follow-up and an average time was 16.5 months (12 to 19 months), all the joints had good or excellent clinical results. Radiographically, the positions of the prostheses were normal, the average limbs length and femoral eccentricity recovered as normal. The average range of motion of the hip improved remarkable, such as flexion improved from (20.1 +/- 8.2) degrees to (85.7 +/- 9.8) (t = 32.86, P < 0.01), abduction improved from (10.2 +/- 4.4) degrees to (41.5 +/- 9.1) degrees (t = 19.34, P < 0.01), adduction improved from (16.3 +/- 8.8) degrees to (40.3 +/- 10.4) (t = 11.00, P < 0.01),external rotation improved from (12.3 +/- 5.2)0 to (42.0 +/- 7.7) degrees (t = 19.96, P < 0.01), internal rotation improved from (3.4 +/- 1.1) degrees to (23.0 +/- 9.8) degrees (t = 12.41, P < 0.01). The Harris score rose from preoperative (39.3 +/- 5.6) to (91.4 +/- 10.3) at the latest follow up (t = 27.75, P < 0.01). CONCLUSION: Short-term results show that metal on metal hip joint prosthesis with large diameter heads has advantages of small deformation of acetabular cup, lower wearing, large range of motion and few dislocation. It offers a newly valuable technology for treatment of osteonecrosis, osteoarthritis, femoral neck fracture and DDH with the higher requirement of movement after the operation.

[Prevention of prothesis dislocation after the revision of total hip arthroplasty].

OBJECTIVE: To explore the role of reconstruction of the posterior capsule and external rotators in prevention of postoperative dislocation in total hip arthroplasty revision following the posterolateral approach. METHODS: Forty-five patients (47 hips) with the mean age of 65 years (55 to 78 years)of failed total hip arthroplasty were revised following the posterolateral approach. Posterior capsule was sutured to the anterosuperior portion of the capsule from where it had been detached, and the external rotators were then reattached to the soft tissue at the tip of the greater trochanter using 1.0 silk suture in surgery. The dislocation rate and risk factors were reviewed retrospectively to determine if closing the posterior capsule resulted in fewer dislocations. The femoral prosthesis and acetabular prosthesis were revised in 29 patients (31 hips), the liner was exchanged in 5 patients (5 hips), and the acetabular prosthesis or femoral components were revised in 10 patients (10 hips) and one patient (one hip) respectively. The procedure was the patient's first revision in 29 patients (30 hips), the second revision in 15 patients (16 hips), and the third revision in one patient(one hip). Radiographic evaluation included lower limb discrepancy, acetabular phase, femoral offset, anteversion angle, prosthetic loosening before and after revision. Function evaluation based on Harris score system. RESULTS: All patients were followed up with an average of 2.7 years. None of the patients sustained dislocation or infection, except one patient felt the anterior instability but without dislocation, X-ray revealed the acetabular component was in excessively anteversion. Lower leg discrepancy, acetabular abduction, anteversion femoral offest and collodiaphyseal angle were restored to normal level after operation on the basis of X-ray. One of the acetabular components and one of the femoral components were loose without dislocation. The Harris hip score improved from (49.13 +/- 15.53) points preoperatively to (83.59 +/- 6.93) points at the final follow-up (P < 0.05). According to Harris functional evaluation, 36 hip got an excellent result, 5 good, 5 fair and 1 bad. CONCLUSION: The historically high dislocation rate with the posterolateral approach for total hip arthroplasty revision can be reduced by careful soft tissue balancing,correction of implant alignment, meticulously closure of the posterior capsule, and reattaching the external rotators.