LncRNA NKILA inhibits the proliferation and promotes the apoptosis of CSCC cells by downregulating miRNA-21.

Long noncoding RNA (lncRNA) NKILA has been well studied in several types of human tumors as a tumor suppressor, while its involvement in cervical squamous cell carcinoma (CSCC) remains unclear. In our studies, we found that serum NKILA was at lower levels and serum microRNA-21 (miRNA-21) was at higher levels in patients with early stage CSCC than in the healthy female. Altered expression of NKILA and miRNA-21 can effectively separate patients with CSCC at an early stage from healthy controls. Serum levels of NKILA were significantly and negatively correlated with miRNA-21 in patients with CSCC but not in normal controls. Overexpression of NKILA mediated the inhibited expression of miRNA-21 in CSCC cells, but mimic transfection of miRNA-21 did not significantly change the expression level of NKILA. Overexpression of NKILA repressed the proliferation and promoted the apoptosis of CSCC cells, while miRNA-21 showed opposite functions. In addition, miRNA-21 mimic transfection reduced the effects of NKILA on CSCC cells. Collectively, lncRNA NKILA could repress the proliferation and promote the apoptosis of CSCC cells by downregulating miRNA-21.

Retrospective analysis of clinicopathological features and prognosis for aggressive angiomyxoma of 27 cases in a tertiary center: a 14-year survey and related literature review.

PURPOSE: Aggressive angiomyxoma (AAM) is a rare and often misdiagnosed tumor that is characterized by frequent local recurrences. This study aimed to investigate the clinicopathological characteristics, surgical experiences, and prognosis for aggressive angiomyxoma to improve the accuracy of diagnosis and develop treatment strategies for decreasing recurrence rates. METHODS: Clinicopathological data and follow-up information for 27 patients with AAM diagnosed and treated at the Shengjing Hospital of China Medical University between January 2006 and October 2019 were retrospectively analyzed. RESULTS: The median age at disease onset among 27 patients was 39 years. The male to female ratio was 1:4.4. Painless and slow-growing mass was the most common symptom. Masses occurring in the perineum and pelvic cavity accounted for 81.5% (22/27). All of the 27 patients underwent surgical treatment. Surgical approaches included transperineal and transvaginal resection. Large pelvic masses were treated with combined abdominoperineal surgery. The postoperative recurrence rate was 37%. Kaplan-Meier survival analysis revealed that 5-year progression-free survival (PFS) rate was 64.4% and the median PFS was 132.0 ± 29.6 (95% CI 72.9-190.1). Multivariate Cox proportional analysis found that surgical margin is an independent prognostic factor for PFS (P = 0.018). None of the patients experienced distant metastasis. CONCLUSIONS: Clinical manifestations of AAM are non-specific. Laboratory testing, imaging examinations, and immunohistochemistry are helpful for diagnosis and differential diagnosis. Surgical approach can be determined according to the relationship between the tumor and adjacent organs and infiltration degree. The development of personalized treatment strategies should aim to achieve a complete resection on the premise of preserving the structure and function of important organs to maintain patient quality of life.

Long noncoding RNA LINC00473 drives the progression of pancreatic cancer via upregulating programmed death-ligand 1 by sponging microRNA-195-5p.

Pancreatic cancer (PC) is a great health burden to patients owing to its poor overall survival rate. Long noncoding RNAs (lncRNAs) interact with microRNAs (miRs) to participate in tumorigenesis. Therefore, we aim to uncover the role and related mechanism of LINC00473 in PC through the modulation of miR-195-5p and programmed death-ligand 1 (PD-L1). Increased LINC00473 and PD-L1 but declined miR-195-5p were determined in PC tissues and cell lines, and it was found that LINC00473 mainly situated in the cytoplasm. Also, miR-195-5p was verified to bind with both LINC00473 and PD-L1. Next, with the aim to examine the ability of LINC00473, miR-195-5p, and PD-L1 on the PC progression, the expression of LINC00473, miR-195-5p and PD-L1 were altered with mimics, inhibitors, overexpression vectors or siRNAs in PC cells and cocultured CD8+ T cells. It was demonstrated that LINC00473 sponged miR-195-5p to upregulate PD-L1 expression. More important, the obtained results revealed that LINC00473 silencing or miR-195-5p upregulation elevated the expression of Bcl-2 associated X protein (Bax), interferon (IFN)-γ, and interleukin (IL)-4 but reduced the expression of B-cell lymphoma-2 (Bcl-2), matrix metalloproteinase (MMP)-2, MMP-9, and IL-10, thus inducing the enhancement of the apoptosis as along with the inhibition of proliferation, invasion, and migration of the PC cells. LINC00473 silencing or miR-195-5p elevation activated the CD8+ T cells. Taken together, LINC00473 silencing blocked the PC progression through enhancing miR-195-5p-targeted downregulation of PD-L1. This finding offers new therapeutic options for treating this devastating disease.

Metastatic patterns and surgical methods for lymph nodes No. 5 and No. 6 in proximal gastric cancer.

OBJECTIVE: The current surgical treatment guidelines for early proximal gastric cancer (PGC) still lack agreement. Lymphadenectomy of lymph nodes No. 5 and No. 6 is the major difference between total and proximal gastrectomy. We elucidated the appropriate surgical procedure for PGC by investigating the pathological characteristics and prognostic significance of lymph nodes No. 5 and No. 6. METHODS: In total, 333 PGC patients who underwent total gastrectomy were enrolled in this study. We investigated their clinicopathological characteristics and the metastatic patterns of the lymph nodes. Patients with metastasis in lymph nodes No. 5 and No. 6 were combined into one group and we compared the difference in survival between those with and without metastasis in lymph nodes No. 5, 6 (lymph nodes No. 5 and No. 6 in any group of metastasis) for different subgroups. RESULTS: The metastatic rates for lymph nodes No. 5 and No. 6 in PGC were 9.91% and 16.11%, respectively. The metastatic rate for both lymph nodes No. 5, 6 was 20.42%. Multivariate analysis showed that positive metastasis in lymph node No. 4, depth of invasion, and tumor size were independently correlated with the presence of metastasis in lymph nodes No. 5, 6. CONCLUSIONS: When lymph node No. 4 is positive (intraoperative pathology) or tumor size ≥5 cm or T4 stage, lymphadenectomy should be performed for lymph nodes No. 5 and No. 6, and total gastrectomy is recommended.

Network Meta-Analysis on the Effects of DNA Damage Response-Related Gene Mutations on Overall Survival of Breast Cancer Based on TCGA Database.

The study was conducted for comparing the effects of 12 DNA damage response gene mutations (CHEK1, CHEK2, RAD51, BRCA1, BRCA2, MLH1, MSH2, ATM, ATR, MDC1, PARP1, and FANCF) on the overall survival (OS) of breast cancer (BC) patients. We searched the Cancer Genome Atlas (TCGA) database from inception to September 2016. Studies that investigated the association between 12 DNA damage responses related genes and BC consolidated into this Network meta-analysis, by comparing directly or indirectly to evaluate the hazard rate (HR) value and the surface under the cumulative sequence ranking curves (SUCRA). In total four articles were involved. Our results demonstrated 12 DNA damage response gene mutations were associated to the poor prognosis of BC patients (CHEK1: HR = 9.9, 95%CI = 3.6-26.0; CHEK2: HR = 6.9, 95%CI = 3.1-15.0; RAD51: HR = 5.8, 95%CI = 2.2-15.0; BRCA1: HR = 2.8, 95%CI = 1.3-6.1; BRCA2: HR = 3.9, 95%CI = 2.0-7.7; MLH1: HR = 11.0, 95%CI = 3.4-33.0; MSH2: HR = 6.5, 95%CI = 2.1-20.0; ATM: HR = 5.6, 95%CI = 2.6-12.0; ATR: HR = 2.9, 95%CI = 1.3-6.9; MDC1: HR = 15.0, 95%CI = 5.0-45.0; PARP1: HR = 3.4, 95%CI = 1.8-6.6; FANCF: HR = 6.0, 95%CI = 1.8-20.0). SUCRA results revealed that the mutation of MDC1 gene was related to the worst prognosis in patients with BC (SUCRA = 17.32%). DNA damage response gene mutations were associated to the poor prognosis in patients with BC and the BC patients with MDC1 gene mutation had the worst prognosis. J. Cell. Biochem. 118: 4728-4734, 2017. © 2017 Wiley Periodicals, Inc.

Histopathology-based prognostic score is independent prognostic factor of gastric carcinoma.

BACKGROUND: The aim of our study was to evaluate the histological characteristics and prognosis of gastric cancer. METHODS: Clinicopathlogical variables of 932 patients with gastric carcinoma admitted to the Department of Surgical Oncology at the First Hospital of China Medical University were analyzed retrospectively. Different histological characteristics of gastric cancer were summarized and assigned score according to the malignancy defined by WHO classification, the scores were stratified into 4 stage, the prognosis of different stages were analyzed by Kaplan-Meier analysis and cox regression. RESULTS: Among the 932 patients, 246 (26.39%) had mixed histology type of gastric cancer. Compared to the pure histological type, mixed histological type of gastric cancer was significant associated with tumor size, lymph node metastasis and depth of invasion (all P < 0.05). The 5-year survival rates of advanced and early gastric cancer patients with mixed type were 40.8% and 83.5% respectively, which were lower than those with pure type (50.0% and 95.8%, P < 0.01). Statistically significant difference with stratification of early and advanced stage could be observed between patients with the histological grading score. The data showed that the histological score could be the independent factor of prognosis. CONCLUSIONS: The histological score is an independent factor of gastric cancer, it exerts an excellent ability to classify survival of patients with gastric carcinoma. It also provides a new strategy and parameter for evaluating the biological behavior and prognosis of gastric cancer.

[Performance of computer-assisted imaging system in detection of squamous intraepithelial lesion of uterine cervix].

OBJECTIVE: To evaluate the performance of computer-assisted imaging system in the detection of cervical squamous intraepithelial lesion and quality-assurance. METHODS: Manual PAP screening (n = 140 580) and image-assisted screening (n = 32 885) were compared for the detection rates of squamous cell abnormalities, the atypical squamous cells (ASC) to squamous intraepithelial lesion (SIL) ratio, the positive rates of high risk human papillomavirus (HR-HPV) test in the case of atypical squamous cells of undetermined significance (ASC-US), and the correlation between cytopathology and histopathology. RESULTS: Compared with manual screening, computer-assisted imaging system showed increased overall positive detection by 0.32%, decreased detection of ASC by 0.21%, increased detection of low-grade squamous intraepithelial lesion (LSIL) by 0.22%, increased detection of high-grade squamous intraepithelial lesion or worse (HSIL) by 0.31%, and decreased ASC to SIL ratio from 2.59 to 1.60. Computer-assisted imaging system did not change the HR-HPV positive rate of the patients who were ASC-US, or the coincidence rate between cytopathology and histopathology. Moreover, the productivity of the laboratory operation increased 58.33%. CONCLUSION: Computer-assisted imaging system significantly increases the overall positive detection rate of cervical SIL, improves accuracy and work efficiency of screening, decreases the ASC/SIL rate, and strengths the quality-assurance of laboratory testing.

[Expression and significance of p-AKT, p-GSK3ß and ß-catenin in epithelial carcinoma of ovary].

OBJECTIVE: To investigate the expressions of phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3ß (p-GSK3ß) and ß-catenin proteins and to evaluate their relationship with the clinical pathological characteristics in epithelial tumors of the ovary. METHODS: The expression of p-AKT, p-GSK3ß, and ß-catenin was detected with immunohistochemical staining (EnVision method) in 10 cases of benign epithelial neoplasia, 10 cases of borderline epithelial neoplasia and 70 cases of ovarian carcinoma. The relationship of the expression of p-AKT, p-GSK3ß and ß-catenin with the clinical pathological features was analyzed. RESULTS: The positive expression rates of p-AKT, p-GSK3ß and ß-catenin in epithelial ovarian carcinoma were 67.1% (47/70), 60.0% (42/70) and 71.4% (50/70), respectively. Compared to the results of benign and borderline epithelial neoplasia, the expression of the three proteins in carcinoma of the ovary was significantly different (all P < 0.05).Positive correlation was found between p-AKT and p-GSK3ß, p-GSK3ß and ß-catenin, and p-AKT and ß-catenin in epithelial ovarian carcinoma (r = 0.546, 0.581, 0.500, respectively; all P < 0.05). Compared to the results of benign and borderline epithelial neoplasia, the expression of p-AKT protein in epithelial ovarian carcinoma was significantly different (all P < 0.05). The expression of p-AKT was correlated with the differentiation of epithelial ovarian carcinoma (P < 0.05), but no relationship was found between its expression and histological classification and FIGO staging (P > 0.05). The expression of p-GSK3ß and ß-catenin in epithelial ovarian carcinoma were both higher than that in benign and borderline epithelial neoplasia (P < 0.05), and correlated with tumor differentiation and FIGO staging (P < 0.05), but no relationship were found between their expression with histological classification (P > 0.05). CONCLUSIONS: Positive correlations are found between p-AKT, p-GSK3ß and ß-catenin in epithelial ovarian carcinoma. The activation of ß-catenin is possibly correlated with inactivation of p-GSK3ß that binds to p-AKT.

PDCD4 regulates apoptosis in human peritoneal mesothelial cells and promotes gastric cancer peritoneal metastasis.

OBJECTIVE: Programmed cell death 4 (PDCD4) is a tumor suppressor gene, however, the function and regulatory mechanism remain to be discovered. The connection between tumorigenesis and apoptosis is one of the most important foci of cancer research. Our study aimed to explore the connections between PDCD4-mediated apoptosis of human peritoneal mesothelial cells (HPMC) and peritoneal metastasis in gastric cancer. METHODS: The PDCD4 expression in 31 pairs of HPMC and tumor tissues was assessed by immunohistochemistry and RT-PCR. In cell experiments, we monitored gastric cancer cell migration with a Transwell chamber assay when PDCD4 was silenced in HPMC. Subsequently, apoptosis of HPMC was detected by a flow cytometric assay and western blotting. After analyzing cytokines in culture supernatants from gastric cancer with enzyme-linked immunosorbent assays (ELISAs), transforming growth factor-beta 1 (TGF-ß1) was abundant in the culture supernatants of gastric cancer. Then, PDCD4 expression in HMrSV5 cells was analyzed by western blotting after retreatment with different concentrations of TGF-ß1. Moreover, apoptosis of peritoneal mesothelial cells treated with TGF-ß1 was detected according to the above methods. RESULTS: In human metastatic peritoneal tissues, the expression of PDCD4 was significantly lower than that in normal tissues. At the same time, decreased expression of PDCD4 in HPMC was associated with increased migration capacity of gastric cancer cells. Moreover, suppressing the expression of PDCD4 promoted apoptosis in mesothelial cells which may be regulated by TGF-ß secreted from gastric cancer cells. CONCLUSIONS: These data suggested that decreased expression of PDCD4 significantly promoted apoptosis in human peritoneal mesothelial cells, thus inducing peritoneal metastasis, and that TGF-ß1 secreted from gastric cancer cells may have played a crucial role.

A novel external esophageal perfusion model for reflux-associated respiratory symptoms.

BACKGROUND AND OBJECTIVE: Gastroesophageal reflux disease (GERD) has been linked to a number of extra-esophageal symptoms and disorders, primarily in the respiratory tract. Current animal models of reflux esophagitis are adapted to diseases of the digestive system, rather than to reflux-associated respiratory symptoms. The aim of this study was to evaluate a novel external esophageal perfusion model to induce esophageal, tracheal and pneumonic histological injury similar to that associated with GERD. METHODS: Twenty guinea pigs were randomized to the acid-treated or PBS-treated group. Esophageal catheters were used to perfuse the esophageal lumen of guinea pigs with hydrochloric acid containing 1 g/l pepsin or PBS for 14 days. The total cell number and cell differential counts in bronchoalveolar lavage fluid (BALF) were determined 24 h after the last perfusion. Histological changes in the esophageal, tracheal and pneumonic tissues were observed by hematoxylin-eosin staining. RESULTS: The numbers of lymphocytes, eosinophils and total inflammatory cells in the BALF were significantly higher in acid-perfused than PBS-perfused animals. Histological evidence suggested esophageal and pneumonic inflammations were prominent in acid-treated animals. CONCLUSION: Repetitive, acid-perfused, esophageal events copied the animal models of reflux esophagitis, and elicited inflammatory responses in the airways and lungs of guinea pigs.

Long non-coding RNA LINC01207 silencing suppresses AGR2 expression to facilitate autophagy and apoptosis of pancreatic cancer cells by sponging miR-143-5p.

Pancreatic cancer is a serious malignancy accompanied by a well-documented poor prognosis. Accumulating studies have indicated the crucial roles played by long non-coding RNAs (lncRNAs) in proliferation, apoptosis and invasion of cancer cells. The aim of the current study was to investigate the role of lncRNA LINC01207 in autophagy and apoptosis of pancreatic cancer cells and its regulatory mechanism interacting with miR-143-5p. Initially, expression profiles of lncRNAs and genes associated with pancreatic cancer were identified. The expression patterns of LINC01207, miR-143-5p and AGR2 in both pancreatic cancer and adjacent tissues were then determined. The binding relationship of LINC01207 to miR-143-5p and targeting relationship of miR-143-5p to AGR2 were subsequently verified. Silencing of LINC01207, or up-regulation or down-regulation of miR-143-5p was introduced into the pancreatic cancer cells, so as to analyze their effects on the cell growth, apoptosis and autophagy. Besides, these regulatory effects were further explored with the determination of the autophagy- and apoptosis-related gene or proteins. LINC01207 and AGR2 were highly expressed while miR-143-5p was poorly expressed in pancreatic cancer. Functionally, LINC01207 can bind to miR-143-5p, and AGR2 was a target gene of miR-143-5p. Importantly, silencing of LINC01207 down-regulated the expression of AGR2 by up-regulating miR-143-5p. Moreover, silencing of LINC01207 and up-regulation of miR-143-5p promoted cell apoptosis and autophagy, corresponding to increased expression of autophagy- and apoptosis-related proteins, in addition to inhibited cell growth. Taken together, silencing of LINC01207 prevents the progression of pancreatic cancer by impairing miR-143-5p-targeted AGR2 expression, providing a potential target for pancreatic cancer treatment.

Fibrosis of mesothelial cell-induced peritoneal implantation of ovarian cancer cells.

BACKGROUND: Peritoneal metastasis frequently occurs in patients with advanced ovarian cancer and is the main basis for a poor prognosis. The mechanism underlying preferential ovarian cancer spread to the peritoneum is not well understood. METHODS: Herein, we investigated the significance and mechanism underlying fibrosis of mesothelial cells promoting peritoneal implantation of ovarian cancer. We have assessed the mesothelial cell fibroblast transformation process in peritoneal tissues of omentum and fibrotic mesothelial cell release of chemokines to promote dissemination by scanning electron microscopy, ELISA, Western blot, and Transwell chamber assay. RESULTS: We showed that the fibrosis of mesothelial cells exists in the peritoneum of ovarian cancer patients with peritoneal metastasis. Fibrosis of the mesothelial cells was induced by TGF-ß1, which upregulates the CXCL12-CXCR4 and CXCL16-CXCR6 axes of mesothelial cells. CONCLUSION: CXCL12-CXCR4 and CXCL16-CXCR6 may be important signaling pathways closely involved in peritoneal metastasis of ovarian cancer that require further investigation. The findings may lead to developing alternative strategies aimed at preventing and treating the metastasis of ovarian cancer.

Synchronous of gastric adenocarcinoma and schwannoma: report of a case and review of literatures.

We presented a case of 80-year-old male with long term stomachache, marasmus and anaemia. Endoscopic evaluation suggested the malignant ulcerative tumor on the Gastric antrum, and biopsy confirmed the diagnosis of gastric adenocarcinoma. Surprisingly, in resected specimen the pathologist found a nodule just below the ulcer with clear boundary and gray-yellow section. Histologically, the whole lesion was composed with adenocarcinoma area and spindle tumor cells area. In the spindle tumor cells area, the cells with round or oval nuclei, eosinophilic cytoplasm, and these cells showed bundle or fence-like arrangement. Immunohistochemistry study presented positive expression of vimentin, S-100 and GFAP, negative expression of SMA, desmin, CD34, CD117 and Dog-1, which suggested the diagnosis of co-occurrence of gastric adenocarcinoma and schwannoma. To our knowledge, it is an extremely rare case that only two cases have been reported.

Flotillin2 expression correlates with HER2 levels and poor prognosis in gastric cancer.

OBJECTIVE: Flotillin gene is known as a tumor promoter or suppressor, depending on the tumor type or tumor stage. We aimed to investigate the clinical significance of flotillin2 protein expression in gastric cancer. METHODS: We examined flotillin2 and erbB2 levels in tissue microarray of 282 gastric cancer samples and analyzed the association between flotillin2 levels, clinicopathologic factors and prognosis. The regulation of erbB2 by flotillin2 was examined with flotillin2 siRNA-transfected gastric cancer cells. RESULTS: Flotillin2 partially co-localized with erbB2 at the plasma membrane as detected by confocal microscopy, levels of erbB2 were reduced after flotillin knockdown in SGC-7901 cancer cells, and the expression of flotillin2 was positively correlated with that of erbB2. In non-neoplastic gastric mucosa, flotillin2 was not expressed in the epithelial compartment. In gastric cancer, positive staining of flotillin2 was shown in 129 (45.7%) of 282 cases, also, it was significantly associated with a Lauren grade, histologic type, lymphovascular invasion and tumor location. Moreover, survival analysis showed that flotillin2 expression was an independent prognostic factor of poor survival (p<0.001). CONCLUSIONS: These results indicate that a positive correlation exists between flotillin2 and erbB2 expression levels, flotillin2 maybe involved in the stabilization of erbB2 at the plasma membrane, flotillin2 is significantly correlated with cancer progression and poor prognosis in gastric cancer.