Low expression of long non-coding RNA GAS5 is associated with poor prognosis of patients with thyroid cancer.

The study aims to investigate the role of long non-coding RNA (lncRNA) GAS5 in the diagnosis and prognosis of patients suffering from thyroid cancer (TC). A total of 212 patients with TC and 61 patients with benign thyroid tumor were enrolled in the study. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the lncRNA GAS5 expression in TC and benign tumor tissues. All TC patients were categorized into high-risk and low-risk groups according to the MACIS, AGES and AMES prognostic scoring system. A 5-year follow-up was conducted in order to determine the disease free survival (DFS) rates and overall survival (OS) rates. The associations between lncRNA GAS5 expression and prognosis of TC patients were analyzed by The Kaplan-Meier survival curves and the Cox regression models. There was a decrease in the lncRNA GAS5 expression in TC tissues in comparison to benign tumor tissues. Expression of lncRNA GAS5 showed significant association with tumor node metastasis (TNM) staging, lymph node metastasis and the multiple cancer foci of TC. AMES high-risk patients showed a decreased expression of lncRNA GAS5 expression than the AMES low-risk patients. The AGES and MACIS high-risk patients showed lower lncRNA GAS5 expression than low-risk patients. The survival rate of TC patients with high lncRNA GAS5 expression was higher than that of TC patients with low lncRNA GAS5 expression during the DFS and OS periods. Cox regression analysis indicated that lncRNA GAS5 expression, TNM staging, lymph node metastasis and multiple cancer foci were independent risk factors for poor prognosis in TC patients. LncRNA GAS5 may be closely related to the diagnosis and prognosis of TC.

Short-term efficacy of different chemotherapy regimens in the treatment of advanced gastric cancer: a network meta-analysis.

OBJECTIVE: A network meta-analysis was performed to compare the short-term efficacy of different chemotherapy regimens in the treatment of advanced gastric cancer. METHODS: Randomized controlled trials of different chemotherapy regimens for advanced gastric cancer were included in this study. Network meta-analysis combined direct evidence and indirect evidence to evaluate the odds ratio and draw surface under the cumulative ranking curves of different chemotherapy regimens in advanced gastric cancer. RESULTS: The results of surface under the cumulative ranking curves showed that S-1 and capecitabine regimens were better than fluorouracil. As for multi-drug combination regimens, the disease control rate of cisplatin + capecitabine, docetaxel + cisplatin + fluorouracil and etoposide + cisplatin + capecitabine regimens were relatively better, while fluorouracil + adriamycin + mitomycin regimen was relatively poorer when compared with cisplatin + fluorouracil regimen. Additionally, the overall response ratio of cisplatin + capecitabine, paclitaxel + fluorouracil, docetaxel + cisplatin + fluorouracil and etoposide + cisplatin + fluorouracil regimens were relatively better, while the disease control rate of fluorouracil + adriamycin + mitomycin regimen was relatively poorer when compared with cisplatin + fluorouracil regimen. Furthermore, the results of cluster analysis demonstrated that cisplatin + capecitabine, etoposide + cisplatin + capecitabine, S-1 + paclitaxel and S-1 + irinotecan chemotherapy regimens had better disease control rate and overall response ratio for advanced gastric cancer patients. CONCLUSION: This network meta-analysis clearly showed that multi-drug combination chemotherapy regimens based on capecitabine and S-1 might be the best chemotherapy regimen for advanced gastric cancer.

PTEN/PI3K/AKT protein expression is related to clinicopathological features and prognosis in breast cancer with axillary lymph node metastases.

We explored the relations between PTEN/PI3K/AKT expression and clinicopathological characteristics and prognosis in breast cancer patients with and without axillary lymph node metastasis (LNM). Tissues and follow-up data from 142 patients with (LNM group) and 154 without (non-LNM group) metastases were collected. Expression of PTEN/PI3K/AKT was detected using immunohistochemistry staining. With axillary LNM, the positive rate of PTEN was reduced, whereas that of PI3K and AKT was increased. Expression of AKT was negatively correlated with PTEN expression but positively correlated with PI3K expression. Apparent correlations were detected between AKT and axillary LNM with a tumor size of 2 cm or less; between PTEN, PI3K, and AKT and axillary LNM in stage T1 or T2 breast cancer and invasive carcinoma of a nonspecial type; and between PTEN and AKT and axillary LNM of histologic grade I or II tumors and non-triple-negative breast cancer (all P<.05). In the LNM group, the 5-year survival rate of patients with PTEN-positive tumors was higher than that of patients with PTEN-negative lesions; whereas in the non-LNM group, the 5-year survival rate of patients with AKT-positive tumors was lower than that of patients with AKT-negative lesions (both P<.05). Cox regression analysis showed that PTEN expression was an independent prognostic factor for patients with LNM; AKT expression, tumor diameter, pathologic grade, and pathologic type were independent prognostic factors for patients without LNM. In conclusion, TEN/PI3K/AKT proteins are related to the clinicopathological features and prognosis of breast cancer with axillary LNM.

A network meta-analysis for toxicity of eight chemotherapy regimens in the treatment of metastatic/advanced breast cancer.

OBJECTIVE: To compare the incidence of toxicity of 8 different chemotherapy regimens, including doxorubicin + paclitaxel, doxorubicin, capecitabine, CMF (cyclophosphamide + methotrexate + 5-fluorouracil), FAC (fluorouracil + doxorubicin + cyclophosphamide), doxorubicin + docetaxel, doxorubicin + cyclophosphamide and paclitaxel in the treatment of metastatic/advanced breast cancer. RESULTS: This network meta-analysis included 8 randomized controlled trials (RCTs). The findings revealed that, with regard to capecitabine alone regimen exhibited higher incidence of nausea/vomiting than doxorubicin + paclitaxel regimen, doxorubicin alone regimen and paclitaxel alone regimen in the treatment of patients with metastatic/advanced breast cancer (OR = 32.48, 95% CI = 1.65~2340.57; OR = 22.75, 95% CI = 1.03~1923.52; OR = 59.63, 95% CI = 2.22~5664.88, respectively). Furthermore, doxorubicin + cyclophosphamide regimen had lower incidence of febrile neutropenia than doxorubicin + docetaxel (OR = 0.17, 95% CI = 0.03~0.96). No significant difference in the incidence of stomatitis was observed among eight chemotherapy regimens. MATERIALS AND METHODS: We initially searched PubMed, Cochrane Library and Embase databases from the founding of these databases to January 2016. Eligible studies investigating the 8 different chemotherapy regimens for treatment of metastatic/advanced breast cancer were included for direct and indirect comparison. The odds ratio (OR) and surface under the cumulative ranking curves (SUCRA) value of the incidence of toxicity among eight chemotherapy regimens were analyzed. CONCLUSIONS: Capecitabine alone regimen and doxorubicin + docetaxel regimen may have a more frequent toxicity in the treatment of metastatic/advanced breast cancer.

Long non-coding RNA ANRIL promotes the invasion and metastasis of thyroid cancer cells through TGF-ß/Smad signaling pathway.

OBJECTIVE: To investigate the effect of antisense non-coding RNA in the INK4 locus (ANRIL) on invasion and metastasis of thyroid cancer (TC). RESULTS: ANRIL expression was significantly up-regulated in TC tissues and cells (P < 0.001), and ANRIL expression was significantly different regarding histological grade and LNM (both P < 0.01). The siRNA-mediated ANRIL silencing inhibits proliferation, invasion, and metastasis of TPC-1 and SW579 cells, and lung metastasis, which can be reversed by TGF-ß1 siRNA. The mRNA levels of p15INK4b, p14ARF and p16INK4a in TPC-1 and SW579 cells increased significantly after silencing ANRIL (all P < 0.001), and TGF-ß1 siRNA could reverse the ANRIL siRNA induced increase of p15INK4b; expressions of TGF-ß1 and p-Smad2/3 were increased after silencing ANRIL (both P < 0.05). MATERIALS AND METHODS: TC and adjacent normal tissues were collected from 105 TC patients. LncRNA ANRIL expressions were detected by qRT-PCR. The siRNA ANRIL and siRNA TGF-ß1 were constructed for TPC-1 and SW579 cell line transfection: si-ANRIL group, si-TGF-ß1 group, si-ANRIL + si-TGF-ß1 group, negative control group and blank group. Effects of ANRIL silencing on proliferation, invasion and metastasis of TC cells was detected by MTT assay, Transwell assay and tail vein injection of nude mice in vitro and in vivo. TGF-ß1 and p-Smad2/3 expressions in TGF-ß/Smad signaling pathway were detected by western blot. CONCLUSIONS: ANRIL may reduce p15INK4B expression through inhibiting TGF-ß/Smad signaling pathway, promoting invasion and metastasis of TC cells, and the silencing of ANRIL inhibits the invasion and metastasis of TPC-1 cells.

Roles of microRNA-124a and microRNA-30d in breast cancer patients with type 2 diabetes mellitus.

The aim of the study is to explore roles of microRNA (miR)-124a and miR-30d in breast cancer (BC) patients with type 2 diabetes mellitus (T2DM). A total of 144 cases of confirmed diagnosed BC with T2DM, T2DM, BC, or healthy people were enrolled. Among them, BC patients with T2DM were regarded as the experiment group (n = 36), patients with T2DM as the Dm group (n = 36), patients with BC as the Bc group (n = 36), and healthy subjects as the healthy group (n = 36). The fasting insulin resistance index, glycosylated hemoglobin, and estradiol were measured. MiR-124a and miR-30d expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The insulin resistance index was significantly higher in the experiment group compared to the other three groups (all P < 0.05). The glycated hemoglobin was in a normal range in the Bc group and healthy group, but was higher in the experiment group and the Bc group compared to that in the healthy group (both P < 0.05). The serum estradiol level was obviously higher in the Bc group compared with that in the Dm group and the experiment group (both P < 0.05). The expressions of miR-124a and miR-30d were positively correlated with insulin resistance index, BMI and glycosylated hemoglobin (miR-124a r = 0.659, r = 0.785, and r = 0.862; miR-30d r = 0.742, r = 0.805, r = 0.765; all P < 0.001). Insulin resistance index was an independent factor for expressions of miR124-a and miR-30d. MiR-124a and miR-30d were correlated with insulin resistance and development of BC with T2DM. Although the mechanism is not clear, miR-124a and miR-30d potentially may be used as therapeutic targets and prognostic markers for BC patients with T2DM.

The molecular mechanisms between metabolic syndrome and breast cancer.

Metabolic syndrome, which is extremely common in developed and some developing countries, is a clustering of at least three of five of the following medical conditions: abdominal obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides, and low high-density lipoprotein levels. It has been proved that there is a strong association between metabolic syndrome and breast cancer. Metabolic syndrome could increase the risk of breast cancer and influence the prognosis of the breast cancer patients. Some characteristic of metabolic syndrome such as obesity and lack of physical exercise are all risk factors for developing breast cancer. The metabolic syndrome mainly include obesity, type 2 diabetes, hypercholesterolemia and nonalcoholic fatty liver disease, and each of them impacts the risk of breast cancer and the prognosis of the breast cancer patients in different ways. In this Review, we focus on recently uncovered aspects of the immunological and molecular mechanisms that are responsible for the development of this highly prevalent and serious disease. These studies bring new insight into the complex associations between metabolic syndrome and breast cancer and have led to the development of novel therapeutic strategies that might enable a personalized approach in the management of this disease.

Polyacrylamide hydrogel injection for augmentation mammaplasty: loss of ability for breastfeeding.

Polyacrylamide hydrogel (PAAG) has been widely used for injection augmentation mammaplasty in Russia, China, and Iran for more than 2 decades. In recent years, it has been advocated as a safe permanent filler for soft-tissue augmentation. However, the complications associated with PAAG injection in soft-tissue augmentation have not been extensively investigated. Augmentation mammaplasty through PAAG injection is associated with some complications. The incidence of infection during breastfeeding was reported to be higher than 50%. Herein, we report 58 cases of infection in breastfeeding women receiving PAAG injection, including 50 with unilateral injection (36 on the right, 14 on the left) and 8 bilateral injection. They experienced large breast autoinflation and some severe symptoms, such as local and systemic fever, breast swelling, nipple bulging, tenderness, and pain, which lead to surgical removal of galactocele or intraprosthetic collection of sterile pus resulting in deformity. Operation and comprehensive measures including removal of the injected material, clearing residual cavity, and pharmacotherapy were carried out to control infection and inflammation for 1 to 2 weeks. In the following 12 months, no relapse or recurrence of residual cavity was noted. Therefore, we do not recommend PAAG injection for augmentation mammaplasty, especially in women intending to breastfeed. Patients undergoing PAAG injection for augmentation mammaplasty should avoid breastfeeding. PAAG injection will cause serious consequences resulting in tissue atrophy and breast resection if inappropriately handled.

Autologous nerve implantation into denervated monkey skin promotes regeneration of Meissner's corpuscle.

BACKGROUND: The aim of this study was to observe the effects of autologous nerve implantation into the denervated finger flap on the regression and regeneration of sensory nerve endings and Meissner's corpuscles. MATERIAL/METHODS: Bilateral nerves of fingers were separated: one was removed and the other was implanted into the denervated finger in the implantation group. In the non-implantation group, both nerves were removed. The ventral skin of fingers was collected for immunohistochemistry and electron microscopy 3, 6, 9 and 12 months after surgery. RESULTS: The nerve endings in the Meissner's corpuscles began to degenerate 3 months after denervation. The elementary structure of Meissner's corpuscles was not significantly altered. Nerve fibers were present around the Meissner's corpuscles, accompanied by growing into its inward. The axons in the denervated nerve disappeared and the Meissner's corpuscles began to atrophy at month 6. More regenerated nerve fibers were observed after nerve implantation, including intensive and thick fibers, accompanied by reinnervation of Meissner's corpuscles. More nerve fibers and a higher proportion of myelinated nerve fibers were noted at month 9 in the implantation group, and the reinnervation was present in the majority of Meissner's corpuscles. Naive myelinated nerve fibers appeared at the caudal end of Meissner's corpuscles. The nerve fibers in the Meissner's corpuscles increased to the normal level at 12 months after nerve implantation. CONCLUSIONS: The implanted nerve regenerated a large amount of free nerve endings, which helped to regenerate simple Meissner's corpuscles via governing previously degenerated corpuscles.

Surgical management of intestinal malrotation in adults.

OBJECTIVE: The aim of this study was to review our experience with diagnosis and surgical management of intestinal malrotation in adult patients. PATIENTS AND METHODS: A retrospective review of the surgical outcome of adults with intestinal malrotation was performed. Twelve patients were observed and treated between July 1996 and July 2006 (4 women and 8 men; the mean age of the patients was 28.5 years). Surgical outcomes, including postoperative complications, deaths, and resolution of preoperative symptoms, were measured. RESULTS: A diagnosis of malrotation was made preoperatively in five patients by upper gastrointestinal contrast study, barium enema, or computed tomography scan. The anomaly was discovered incidentally at laparotomy in seven patients. All cases were proved to be malrotation intraoperatively. Nine patients underwent laparotomy and three underwent laparoscopic surgery (one converted to an open procedure). Follow-up ranged from 2 months to 118 months. Three patients had complications: one had wound infection, one had delayed gastric emptying, and one developed adhesive ileus. There were only two recurrences detected and one patient with recurrence required reoperation. No one died. CONCLUSIONS: Intestinal malrotation is a rare but important cause of abdominal pain in adults. It may present with chronic or acute symptoms. Laparotomy and laparoscopy are alternative and feasible techniques with low rates of complications for the treatment of intestinal malrotation in adults.

[Effects of p53 inhibitor-alpha on the proliferation and apoptosis in large intestinal epithelial cells damaged by hyperthermic chemotherapy].

OBJECTIVE: To investigate the effects of p-fifty three inhibitor-alpha (PFT-alpha), a p53 inhibitor, on the proliferation and apoptosis of colon epithelial cells damaged by hyperthermic chemotherapy. METHODS: Normal epithelial cells were obtained from the mucosa at least 10 cm away from the cancer tissue in a specimen of large intestine cancer resected during operation and cultured. PFT-alpha at different concentrations was added into the culture fluid to observe its effects on the proliferation of the epithelial cells. Epithelial cell in logarithmic growth phase were inoculated in 6-well plate and divided into 3 groups: normal control (CON) group; hyperthermic chemotherapy (HTC) group, undergoing treatment of cisplatin and bath in water at 43 degrees C; and PFT-alpha + HTC group, undergoing treatment of PFT-alpha at different concentrations, cisplatin, and warm water bath. The cell apoptosis was observed by annexin V-fluorescein isothiocyanate/propidium iodide (PI) staining and flow cytometry (FCT). The cell cycle was observed by PI staining and FCT. Western blotting was used to detect the protein expression of cyclinB1 and Cdc2, and RT-PCR was used to detect the mRNA expression of cyclinB1. RESULTS: PFT-alpha at the concentration > 60 micromol/L significantly inhibited the proliferation of the large intestine epithelial cells. The natural apoptosis rate of the large intestine epithelial cells (CON group) was 2.9% +/- 0.4%, the apoptosis rate was 27.0% +/- 2.1% in the HTC group, and the apoptosis rates of the PFT-alpha + HTC group were 14.8% +/- 1.5%, 9.7% +/- 1.2%, 6.1% +/- 1.3%, and 3.8% +/- 0.3%, on a downward trend, corresponding to the increase of PFT-alpha concentration from 0, 20, 30, to 40 micromol/L (all P < 0.05). The G(0)/G(1) phase rate of epithelial cells was higher and the S phase rate was lower significantly in the PFT-alpha + HTC group. The G(2)/M phase rate was higher since the PFT-alpha concentration reached 10 micromol/L and then increased along with the increase of the PFT-alpha concentration; the S phase rates of the PFT-alpha + HTC group with different PFT-alpha concentrations were all significantly higher than that of the HTC group (all P < 0.01), however, were still lower than that of the CON group (all P < 0.01). The protein expressions of cyclinB1 and Cdc2 in the PFT-alpha + HTC group were both significantly higher than those in the CON and HTC groups (all P < 0.01), without a significant difference between the latter 2 groups. The mRNA expression of cyclinB1 in the PFT-alpha + HTC group increased along with the increase of the PFT-alpha concentration, and there wee significant differences in the mRNA expression of cyclinB1 between the CON and PFT groups and PFT-alpha + HTC group with the PFT-alpha concentration > or = 10 micromol/L (P < 0.05 or P < 0.01). CONCLUSION: PFT-alpha dose-dependently protects the hyperthermic chemotherapy-induced damage to the large intestine epithelial cells via upregulation of protein and mRNA expression of cyclinB1, increasing the phosphorylation level of Cdc2, decreasing the cyclinB1/Cdc2 activity, and increasing the G(2)/M phase rate of the cells.

[Changes in glucocorticoid receptor and heat shock protein 70 in liver tissue after trauma with hemorrhagic shock in rats].

OBJECTIVE: To investigate changes and functions of glucocorticoid (GR) and heat shock protein 70 (HSP70) at the level of cellular receptor in liver in hemorrhagic shock after trauma. METHODS: Adult Wistar rats were used and a rat model of shock was reproduced by hemorrhaging accompanied by bilateral femur fracture. Changes in hepatic tissue GR, HSP70, pathology of liver, hepatic function markers in serum were dynamically observed. The expression of GR and HSP70 in hepatic tissue was assayed by Western blot and then analyzed with computer imaging system. RESULTS: Protein content of GR gradually decreased in hepatic tissue after trauma, reduced to the nadir at 6 hours after trauma, and it was decreased even more when trauma was added to bleeding. Protein content of HSP70 was gradually increased in hepatic tissue after severe trauma, peaking at 6 hours after trauma, and it maintained at a rather high level at 8 hours after trauma. It was even more increased in when hemorrhagic shock was followed by trauma. Alterations in hepatic function markers and pathology were not obvious after simple trauma. But after trauma was added to hemorrhagic shock, significant increase in alanine aminotransferase (ALT) and total bilirubin (TB) in serum was noted at 4 and 2 hours after trauma respectively (all P<0.01), and albumin content was obviously decreased (P<0.01). There were more inflammatory cell infiltrations in hepatic sinusoids at 6 hours after trauma. CONCLUSION: GR may play an important role in anti-injury mechanism of hepatic tissue cell after trauma with hemorrhagic shock. HSP70 may participate in initiating anti-injury mechanism of hepatic cells.

[Study on the relationship of heat shock protein 70 with secondary liver damage in early stage after severe multiple injury].

OBJECTIVE: To study the action of heat shock protein 70 (HSP70) in the course of secondary hepatic injury in rats in the early stage after multiple injury. METHODS: Adult male Wistar rats were used and rat model was produced by adopting severe thoracic impact injury in accompany with mono femur fracture. Changes of the content of HSP 70 in the hepatic tissue, hepatic function markers in serum were dynamically observed as well as 24 hours mortal rate after severe multiple injury, trauma with glucocorticoid receptor(GR) blocked. The expression of HSP70 in hepatic tissue was assayed by western blot and then analyzed with computer imaging system. RESULTS: The content of HSP70 gradually increased in hepatic tissue after severe trauma, increased to the highest at 8 hours after trauma, and maintained rather high level at 24 hours after trauma. But the alterations of hepatic function markers in serum were not obvious after trauma. After usage of GR blocking agent, The content of HSP70 was much higher than simple trauma group. Alanine aminotransferase (ALT) and total bilirubin (TB) in serum obviously increased in early stage after trauma (both P<0.01), albumin content obviously decreased(P<0.01), while 24 hours mortal rate obviously increased (P<0.01). CONCLUSION: HSP70 may participate in starting a anti-injury mechanism of hepatic tissue cell. But excessive expression of HSP70 may cause injury to liver after severe multiple injury. HSP70 can be identified as an important marker of liver injury and anti-injury after severe multiple injury.