HIF1A-AS2 Promotes the Proliferation and Metastasis of Gastric Cancer Cells Through miR-429/PD-L1 Axis.

BACKGROUND: Gastric cancer (GC) is a common leading cause of cancer-related mortality of all malignancies. LncRNA hypoxia-inducible factor-1 alpha antisense RNA-2 (HIF1A-AS2) has been identified to involve in the development of GC. Therefore, we further explored the detailed molecular mechanism of HIF1A-AS2 in GC progression. METHODS: The expression of HIF1A-AS2, microRNA-429 (miR-429), and programmed cell death ligand 1 (PD-L1) was measured using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell proliferation, migration, and invasion abilities were detected by Cell Counting Kit-8 (CCK-8) or transwell assay. The interaction between miR-429 and HIF1A-AS2 or PD-L1 was confirmed by luciferase reporter assay. Murine xenograft model was established to investigate the role of HIF1A-AS2 in vivo. RESULTS: HIF1A-AS2 was elevated in GC tissues and cell lines. Functional experiments showed that HIF1A-AS2 knockdown inhibited GC cell proliferation, migration, and invasion in vitro, as well as hindered tumor growth in vivo. Moreover, HIF1A-AS2 directly bound to miR-429 based on bioinformatics prediction and luciferase assay, and inhibition of miR-429 abolished the effects of HIF1A-AS2 knockdown on GC cells. Furthermore, miR-429 directly targeted PD-L1, and overexpression of miR-429 suppressed GC tumorigenesis via PD-L1. Besides that, PD-L1 also performed an oncogenic role in GC cell proliferation and metastasis. Additionally, HIF1A-AS2 could indirectly regulate PD-L1 expression via sponging miR-429. CONCLUSION: HIF1A-AS2 is a dependable predictor of malignancy and prognosis in GC and functions as an oncogene to promote GC cell proliferation and metastasis by regulating miR-429/PD-L1 axis, indicating a new insight into the search for novel biomarkers and therapeutic strategies.

Influence of obesity on short- and long-term outcomes after laparoscopic distal gastrectomy for gastric cancer.

PURPOSE: Despite the increasing prevalence of obesity and gastric diseases, the impact of obesity on short- and long-term outcomes of laparoscopic distal gastrectomy for gastric cancer still remains unclear. METHODS: Sixty-one consecutive obese patients with body mass index (BMI)≥30 kg/m2, who underwent laparoscopic distal gastrectomy, were compared with 76 non-obese patients with BMI<30 kg/m2. Short- and long-term outcomes were analyzed in both groups. RESULTS: Obesity was associated with a longer operative time and a greater estimated blood loss. The rate of conversion to open distal gastrectomy was similar between the two groups. There were no 30-day postoperative deaths in either group. There was no significant difference in the overall number or severity of 30-day postoperative complications between the two groups. Regarding long-term survival outcomes, there was no statistical difference in overall (OS) or disease-free survival (DFS) between the two groups. Multivariate analysis showed that BMI did not influence prognosis. CONCLUSION: Laparoscopic distal gastrectomy appears to be a safe and reasonable option for selected obese patients with gastric cancer and results in short- and long-term outcomes similar to those in non-obese patients.

LncRNA SNHG22 promotes gastric cancer progression by regulating the miR-101-3p/e2f2 axis.

Gastric cancer (GC) still poses a significant threat to human life. Hence, there is an urgent need to understand the mechanism of GC progression and develop novel therapeutics approach to treating GC. This study was conducted to evaluate the role of the lncRNA SNHG22 in the progression of GC. First, GC data from TCGA were analyzed using GEPIA. After the starbase database was used to predict SNHG22 target miRNA and miR-101-3p target mRNA. The predictions were validated using a dual-luciferase reporter assay, biotinylated RNA pull-down assay, and RIP-qRT-PCR. The relative expression of SNHG22, miR-101-3p, and E2F2 was measured by qRT-PCR and western blot (WB) analysis, while the mechanism of GC cell proliferation was elucidated through the colony formation and CCK-8 assay. Our result showed that SNHG22 was upregulated significantly in GC tissue samples from TCGA database, GC cell lines, and clinical tissue samples, and its expression was related to low survival rate of gastric cancer patients. Bioinformatics prediction predicted miR-101-3p as the potential target of SNHG22 and E2F2 genes as miR-101-3p target mRNA. We found that E2F2 expression was negatively associated with overall survival of GC patients. Functional study showed that silencing SNHG22 markedly inhibited the proliferation, migration, and invasion of GC cells as well as in vivo tumor growth. This was reversed after inhibiting miR-101-3p or overexpressing E2F2. The lncRNA SNHG22 promotes the proliferation, migration, and invasion of GC cells via the miR-101-3p/E2F2 axis. SNHG22 might be a potential prognostic indicator in gastric cancer.

Fibroadenoma in axillary ectopic breast.

Axillary lumps are common clinical presentations in surgery, which have various differential diagnoses. We encountered an unusual case of an isolated axillary mass. The patient was a young woman in her 20s with a 2 year history of right axillary swelling. Clinically, the lump measured 3 cm ×3 cm, mobile, non-tender, and there was no associated breast lump or skin changes. Our initial impression was an isolated lymphadenopathy, and further workup for tuberculosis lymphadenopathy returned negative. Ultrasound demonstrated a well circumscribed oval lesion, and fine needle aspiration could only identify a benign proliferative breast tissue. As it was increasing in size and causing discomfort, we decided for an excision biopsy for both diagnostic and therapeutic reasons. Intraoperatively, the lump was noted to have well defined, smooth surface along with whitish-grey appearance. The tissue surrounding it was also removed and sent for histopathological assessment. Results confirmed our diagnosis of fibroadenoma in an ectopic breast tissue.

Desmoid fibromatosis infiltrating left adrenal gland and kidney.

Desmoid fibromatosis is a rare, benign, locally aggressive fibroblastic proliferation that may occur in almost any anatomical location. Due to its rarity and unpredictable clinical course, there has not been a standard guideline of treatment. We encountered a case of desmoid fibromatosis in our centre. A young lady previously fit and well was referred for a symptomatic, rapidly growing left sided abdominal mass. Otherwise, she denied any bowel related symptoms or constitutional manifestation. Imaging demonstrated a large well-defined lobulated solid-cystic mass extending from vertebral level T10 to L5, measuring 10.5 cm × 15 cm × 23 cm. The mass was in close proximity with the left adrenal gland, left kidney, pancreas and spleen. Ultrasound guided biopsy interpreted it as a fibroblastic or myelofibroblastic tumour, favouring desmoid fibromatosis. Surgery was then performed where the mass was removed along with the left adrenal gland and kidney. Post-operative care was complicated with pulmonary embolism, hospital-acquired pneumonia and pancreatitis.

A rare case of azygous vein aneurysm with cotriatrium dextrum.

Azygous vein aneurysm (AVA) is an infrequent entity for posterior mediastinal lesion and paratracheal mass. Usually asymptomatic, AVA is discovered during routine examination of a patient. The patho-etiology of the azygous vein aneurysm has not been fully understood till date, making it difficult to postulate the most common cause for its occurrence. Nonetheless, AVA has to be taken into consideration as a differential diagnosis for posterior mediastinal mass or right paratracheal lesion. The objective of this paper is to report a rare case of AVA and further discuss on its patho-etiology leading to the dilatation of azygous vein aneurysm.

Androgen attenuates antitumor effects of gastric cancer cells by bone marrow mesenchymal stem cells via restricting the JNK signaling activation.

BACKGROUND: Researches on bone marrow mesenchymal stem cells (BMMSCs) have generated controversial results in tumor research. In the present study, we aimed to explore the functions of BMMSCs on gastric cancer and the possible mechanism in a mimicking microenvironment of the stomach. METHODS: Transwell co-cultured system was used to co-culture BMMSCs and gastric cancer SGC-7901 cells. In some experiments, androgen and its antagonist were added into the cells as required. Cell viability, cell apoptosis, mRNA and protein expressions of apoptosis- and JNK signaling- associated genes were respectively determined by performing cell counting kit-8, flow cytometry, quantitative real-time PCR and western blot. RESULTS: Androgen contributed to the growth of BMMSCs and SGC-7901 cells. In co-cultured system, BMMSCs not only suppressed SGC-7901 cell viability, induced cell apoptosis and promoted tumor necrosis factor (TNF)-α release, but also regulated the level of Bax/Bcl-2 and elevated the expressions of phosphorylation (p)-JNK and p53. After adding androgens, the anti-tumor effects of BMMSCs were weakened. Meanwhile, the antagonists of androgens could partially recover BMMSCs in vitro inhibitory effects on gastric cancer cells by activation of JNK signaling. CONCLUSIONS: This study demonstrated the important roles of BMMSCs on the growth and apoptosis of gastric cancer cells in vitro. Additionally, in the mimicking microenvironment of the stomach, androgen weakened the antitumor effects of BMMSCs by limiting JNK signaling activation, suggesting that androgen antagonist may be a promising adjuvant drug to BMMSCs in gastric cancer therapy.

Relationship between the expressions of PD-L1 and tumour-associated fibroblasts in gastric cancer.

Previous studies have focused on the changes of tumour cells in immune escape, and less is known about the effect of tumour microenvironment (TME) on immune escape. Tumour-associated fibroblasts (TAF) is an important part of the TME and has special physiological and biochemical characteristics, but the specific mechanism has not been clarified. In order to investigate the effect of TAF on the expression of PD-L1 in gastric cancer cells, gastric cancer cell lines MNK45, SGC7901 were non-contact co-culturing with TAF 1, 3 and 7 d via transwell. PD-L1 mRNA and protein expression were detected using qRT-PCR and FCM. Then, 95 cases of gastric cancer tissues were selected and evaluated PD-L1 and TAF expressions by immunohistochemical examination. The results showed that the mRNA and protein expression of PD-L1 in the experiment group were significantly higher than that in the control group. PD-L1 expression was associated with massive lymphocyte infiltration, diffuse/mixed histology and intratumoral TAFs in gastric cancers. In conclusion, TAFs promoted the growth in gastric cancer cell lines by increased the PD-L1 expression.

Analysis of distinct long noncoding RNA transcriptional fingerprints in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies with the worst prognosis. Recent studies have demonstrated that long noncoding RNAs (lncRNAs) play critical roles in tumorigenesis and cancer progression. However, the expression pattern and roles of lncRNAs in the development of PDAC remain unknown. Herein, we globally analyzed the lncRNA expression profile in human PDAC and non-tumor tissues using four independent public microarray datasets from Gene Expression Omnibus (GEO). The analysis of GEO datasets by repurposing microarray probes confirmed that hundreds of lncRNAs are differentially expressed in PDAC tissues compared with normal tissues. We selected four lncRNAs including LINC00152, CASC9, LINC00226 and F11-AS1 for validation in PDAC cell lines and normal cells. Loss of function assays were performed to investigate the roles of LINC00152 and CASC9 in PDAC cell proliferation and invasion. Taken together, our findings demonstrate lncRNA expression alterations in PDAC and may provide new potential molecular markers for PDAC patient diagnosis and treatment.

Preventing necrotizing enterocolitis by food additives in neonates: A network meta-analysis revealing the efficacy and safety.

BACKGROUND: Necrotizing enterocolitis (NEC) is a serious multifactorial gastrointestinal disease which is often discovered in premature infants. Various additives have been used to prevent NEC; yet, their relative efficacy and safety remain disputed. This study aims to compare the efficacy and safety of 5 food additives, namely, probiotics, probiotics + fructo-oligosaccharides, pentoxifylline, arginine, and lactoferrin in preventing NEC in neonates. METHODS: Embase, PubMed, and Cochrane Library had been searched for all eligible randomized control trials. Odds ratios (ORs) were estimated for dichotomous data and mean differences with 95% credible intervals (CrIs) were estimated for continuous data. Surface under the cumulative ranking curve was used to rank efficacy and safety of the prevention methods on each endpoint. RESULTS: A total of 27 eligible studies with 4649 preterm infants were included in this network meta-analysis (NMA), and the efficacy and safety of 5 food additives were evaluated. Probiotic and arginine exhibited better preventive efficacy compared with placebo (OR = 0.50, 95% CrIs: 0.32-0.73; OR = 0.30, 95% CrIs: 0.12-0.73, respectively). Only probiotic achieved a considerable decrease in the risk of mortality compared to placebo (OR = 0.68, 95% CrIs: 0.46-0.98). NEC patients with lactoferrin appeared to have lower incidence of sepsis than those of placebo (OR = 0.13, 95% CrIs: 0.03-0.61) or probiotic (OR = 0.18, 95% CrIs: 0.03-0.83). CONCLUSION: Based on this NMA, probiotics had the potential to be the most preferable additive, since it exhibited a significant superiority for NEC and mortality as well as a relatively balanced performance in safety.

Partner of Sld five 3: a potential prognostic biomarker for colorectal cancer.

BACKGROUND: Partner of Sld five 3 (PSF3) is a member of the evolutionarily conserved heterotetrameric complex "Go-Ichi-Ni-San" (GINS), which consists of SLD5, PSF1, PSF2, and PSF3. Previous studies have suggested that some GINS complex members are upregulated in cancer, but the status of PSF3 expression in colorectal cancer has not been investigated. METHODS: We investigated the status of PSF3 expression in 137 consecutive resected colorectal caners by quantitative reverse-transcription polymerase chain reaction. Univariable and multivariable Cox regression analyses were performed to assess independent prognostic factors for overall survival in colorectal cancer. RESULTS: In 137 restected colorectal cancer samples, median messenger RNA (mRNA) expression levels of PSF3 were significantly higher in tumor tissues (1.35 × 10(-3), range 2.88 × 10(-4) to 3.16 × 10(-2)) than in adjacent normal tissues (2.94 × 10(-4), range 5.48 × 10(-5) to 1.27 × 10(-3)) (P < 0.05). Moreover, high expression of PSF3 in tumor tissues was associated with shorter disease-free survival and overall survival. When analyzed with a Cox regression model, the PSF3 expression was an independent prognostic factor for overall survival. In addition, in patients with early stage (stage I and II) colorectal cancer, the overall survival rate of the high PSF3 expression group was significantly lower than that of the low PSF3 expression group (P < 0.001). CONCLUSIONS: The PSF3 expression plays an important role in the progression of colorectal cancer and acts as a factor significantly affecting the prognosis of patients. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_217.