Cross-talk between the gut microbiota and monocyte-like macrophages mediates an inflammatory response to promote colitis-associated tumourigenesis.

OBJECTIVE: Macrophages are among the most abundant cells in the colon tumour microenvironment, and there is a close relationship among monocytes, macrophages and the gut microbiota. Alterations in the gut microbiota are involved in tumour development, but the underlying mechanisms remain unclear. We aim to elucidate the temporal changes in macrophage subsets and functions, and how these dynamics are regulated by microbial cues in the initiation of colitis-associated cancer. DESIGN: A mouse model of colitis-associated tumourigenesis was established to determine macrophage dynamics. The role of monocyte-like macrophage (MLM) was confirmed by targeting its chemotaxis. The effects of the gut microbiota were assessed by antibiotic treatment and faecal microbiota transplantation. RESULTS: A selective increase in MLMs was observed in the initial stages of colitis-associated cancer, with an enhanced secretion of inflammatory cytokines. MLM accumulation was regulated by CCL2 expression of colonic epithelial cells, which was influenced by bacteria-derived lipopolysaccharide (LPS). LPS further stimulated interleukin 1ß production from MLMs, inducing interleukin-17-producing T-helper cell activation to promote inflammation. These observations were also supported by altered microbial composition associated with human colitis and colorectal cancer, evolving transcriptional signature and immune response during human colitis-associated tumourigenesis. CONCLUSIONS: The gut microbiota uses LPS as a trigger to regulate MLM accumulation in a chemokine-dependent manner and generate a precancerous inflammatory milieu to facilitate tumourigenesis.

Antibiotic resistance of Helicobacter pylori to 16 antibiotics in clinical patients.

BACKGROUND: Resistance of Helicobacter pylori (H. pylori) to antibiotics is increasing worldwide. To determine the status of H. pylori resistance and its patterns in clinical patients, an investigation utilizing susceptibility testing for commonly used antibiotics was needed. METHODS: Total of 2283 H. pylori strains were collected from 2013 to 2016. The resistance and its patterns of these strains were tested by agar dilution method. The resistance rate and minimal inhibition concentration (MIC) in different gender groups were also analyzed. RESULTS: The overall resistance rates were as following: amoxicillin (1.58%), clarithromycin (22.73%), levofloxacin (24.75%), furazolidone (1.49%), doxycycline (9.20%), cefetamet (97.20%), ceftriaxone (49.60%), cefuroxime (25.20%), gentamicin (3.73%), azithromycin (85.60%), rifampicin (2.80%), metronidazole (92.53%), ornidazole (94.27%), tinidazole (87.20%), ciprofloxacin (43.20%), and moxifloxacin (38.53%). There were only 64.08% strains pan-susceptible to amoxicillin, clarithromycin, levofloxacin, and furazolidone, followed by mono resistance (23.17%), double resistance (11.13%), triple resistance (1.36%), and quadruple resistance (0.26%). Significant differences in the resistance rate and MIC were also observed in different gender groups. CONCLUSION: Antibiotic resistance trends of H. pylori is increasing in clinical patients. With the increasing resistance, it is imperative to individualized therapy based on the results of drug susceptibility testing.

Using gastric juice lncRNA-ABHD11-AS1 as a novel type of biomarker in the screening of gastric cancer.

Long noncoding RNAs (lncRNAs) play vital roles in tumorigenesis. However, the diagnostic values of most lncRNAs are largely unknown. To investigate whether gastric juice lncRNA-ABHD11-AS1 can be a potential biomarker in the screening of gastric cancer, 173 tissue samples and 130 gastric juice from benign lesion, gastric dysplasia, gastric premalignant lesions, and gastric cancer were collected. ABHD11-AS1 levels were detected by reverse transcription-polymerase chain reaction. Then, the relationships between ABHD11-AS1 levels and clinicopathological factors of patients with gastric cancer were investigated. The results showed that ABHD11-AS1 levels in gastric cancer tissues were significantly higher than those in other tissues. Its levels in gastric juice from gastric cancer patients were not only significantly higher than those from cases of normal mucosa or minimal gastritis, atrophic gastritis, and gastric ulcers but also associated with gender, tumor size, tumor stage, Lauren type, and blood carcinoembryonic antigen (CEA) levels. More importantly, when using gastric juice ABHD11-AS1 as a marker, the positive detection rate of early gastric cancer patients was reached to 71.4 %. Thanks to the special origin of gastric juice, these results indicate that gastric juice ABHD11-AS1 may be a potential biomarker in the screening of gastric cancer.

lncRNA-AC130710 targeting by miR-129-5p is upregulated in gastric cancer and associates with poor prognosis.

Long noncoding RNAs (lncRNAs) play an important role in cancer occurrence and development. However, there is largely unknown about lncRNAs significance in the diagnosis and treatment of gastric cancer. In our study, we focused on AC130710, one of lncRNAs. Gastric cancer tissues and adjacent tissues were gathered from 78 patients with gastric cancer. The AC130710 levels were detected by reverse transcription polymerase chain reaction (RT-PCR). Then, we further analyzed the association between AC130710 level and the clinicopathological factors of patients with gastric cancer. Finally, the molecular mechanism underling AC130710 highly expressed in gastric cancer cells was explored. The results showed that AC130710 in cancer tissues from patients with gastric cancer was significantly higher than those in adjacent noncancerous tissues (P < 0.05). Its expression level was significantly associated with tumor size (P = 0.013), tumor-node-metastasis (TNM) stages (P = 0.030), and distal metastasis (P = 0.018). AC130710 expression in MGC-803 was significantly higher than that in normal gastric mucosa cell line GES-1 (P < 0.001). Moreover, miR-129-5p may play an important role in the downregulation of AC130710 in gastric cancer cells. These results indicated that lncRNA-AC130710 may be a potential tumor marker for gastric cancer prognosis.

Androgen Receptor in Breast Cancer: From Bench to Bedside.

Breast cancer (BC) is one of the most common malignancies and the leading cause of cancer-related mortality in women. Androgen receptor (AR) is frequently expressed in diverse BC subtypes. Accumulating evidence has revealed that AR might be a predictive or prognostic factor and a drug target in BC. AR expression and AR pathways differ in various BC subtypes, thereby resulting in controversial inferences on the predictive and prognostic value of AR. Herein, we summarized the roles of AR in different BC subtypes and AR-targeting therapies based on preclinical and clinical studies. Moreover, we highlighted the possible efficacy of a combination therapy via exploiting the AR-related mechanisms and the research on therapeutic resistance.

γδ T Cells: Crosstalk Between Microbiota, Chronic Inflammation, and Colorectal Cancer.

Increasing evidence suggests that intestinal microbiota dysbiosis and chronic inflammation contribute to colorectal cancer (CRC) development. γδ T cells represent a major innate immune cell population in the intestinal epithelium that is involved in the maintenance of gut homeostasis, inflammation regulation, and carcinogenesis. The important contributions of γδ T cells are (i) to perform a protective role in the context of barrier damage and pathogenic microorganism translocation; (ii) to exert either pro- or anti-inflammatory effects at different inflammatory stages; and (iii) to boost the crosstalk between immune cells and tumor microenvironment, inducing a cascade of suppressive immune responses. Understanding the crucial role of γδ T cells would enable us to manipulate these cells during the CRC sequence and improve the efficacy of tumor therapy.

Regulatory mechanisms of long noncoding RNAs on gene expression in cancers.

Long non-coding RNAs (lncRNAs) are a heterogeneous class of RNAs that are non-protein coding transcripts longer than 200 nucleotides. In this review, we introduce the mechanisms by which lncRNAs regulate gene expression in four parts, epigenetic regulation (genetic imprinting and chromatin remodeling), transcriptional regulation (molecular decoy), post-transcriptional regulation (splicing and mRNA decay), and translational regulation. H19, Xist, and others are involved in genomic imprinting. HOTAIR and ANRIL function in chromatin remodeling. GAS5 is degraded through an RNA decay pathway. NEAT1 and MALAT1 function not only in the regulation of transcription but also in splicing.

Global circular RNA expression profile of human gastric cancer and its clinical significance.

Circular RNAs (circRNAs) are a new class of noncoding RNAs. However, the expression profile and clinical significance of circRNAs in human gastric cancer is unclear. The global circRNA expression profile in human gastric cancer was measured by circRNA microarray. Hsa_circ_0014717, one of the most downregulated circRNAs in microarray, was selected as a targeted circRNA to explore its levels in gastric tissues and gastric juice. Freeze-thaw experiment and incubation experiment confirmed the stability of gastric juice circRNAs. A total of 308 circRNAs, including 107 (34.74%) upregulated and 201 (65.26%) downregulated circRNAs, were found significantly aberrantly expressed in gastric cancer tissues. The top ten upregulated in gastric cancer tissues were hsa_circ_0035445, hsa_circ_0003789, hsa_circ_0063809, hsa_circ_0074362, hsa_circ_0006282, hsa_circ_0011107, hsa_circ_0084606, hsa_circ_0005556, hsa_circ_0050547, and hsa_circ_0006470, while the top ten downregulated ones were hsa_circ_0007099, hsa_circ_0001897, hsa_circ_0007707, hsa_circ_0008832, hsa_circ_0001546, hsa_circ_0002089, hsa_circ_0004680, hsa_circ_0000154, hsa_circ_0004458, and hsa_circ_0008394. The hot-point chromosomes were chr1, chr2, chr3, chr9, and chr17. Hsa_circ_0014717 was significantly downregulated in 77.2% (74/96) gastric cancer tissues. Its levels in gastric cancer tissues were related to tumor stage (P = 0.037), distal metastasis (P = 0.048), tissue carcinoembryonic antigen (P = 0.001), and carbohydrate antigen 19-9 expression (P = 0.021). More importantly, hsa_circ_0014717 can stably exist in human gastric juice; and its nature meets the requirements of clinical detection. Our study uncovered the circRNA expression profile in human gastric cancer. Moreover, some circRNAs can stably exist in human body fluid, and has the potential to be used as novel biomarkers for the screening of high-risk gastric cancer patients.

Roles of long noncoding RNAs in gastric cancer and their clinical applications.

PURPOSE: Gastric cancer ranks as the most common cancer in the world. However, the progresses of its diagnosis and treatment are still not satisfactory. The purpose of this study is to summarize the roles of lncRNAs associated with gastric cancer. METHODS: We searched lncRNAs associated with gastric cancer in PubMed. RESULTS: Long noncoding RNAs (lncRNAs), transcripts larger than 200 nucleotides, regulate gene expression at various levels. They are playing important roles in the occurrence and development of gastric cancer. They are involved in signaling pathways, crosstalk with microRNAs, and affecting metastasis by regulating epithelial-to-mesenchymal transition. By acting as oncogenes or tumor suppressors, lncRNAs contribute to gastric cancer occurrence and development. Several lncRNAs including HOTAIR, HULC, LINC00152, MALAT2, H19, GHET1, and GACAT3 have been demonstrated having oncogene activities, while other lncRNAs including LEIGC, GAS5, and FER1L4 have been thought as tumor suppressors. CONCLUSIONS: Several lncRNAs from tissue, blood, and gastric juice have shown potential values in gastric cancer diagnosis or prognosis evaluation.

Plasma lncRNA-GACAT2 is a valuable marker for the screening of gastric cancer.

Long non-coding RNAs (lncRNAs) are crucial in contributing to gastric tumorigenesis and development. However, the diagnostic value of the majority of lncRNAs in gastric cancer (GC) are not clear. The present study investigated the diagnostic value of gastric cancer associated transcript 2 (GACAT2), a lncRNA that is aberrantly expressed in GC tissues. A total of 343 plasma samples from 80 healthy individuals, 29 patients with gastric dysplasia (GD) and 117 paired preoperative and postoperative patients with GC were collected. Plasma GACAT2 levels were subsequently measured by reverse transcription-quantitative polymerase chain reaction. Finally, the associations between plasma GACAT2 levels and various clinicopathological features of patients with GC were assessed. The results demonstrated that plasma GACAT2 levels in preoperative patients with GC were significantly higher than those in the postoperative group (P=0.031). Compared with healthy individuals, plasma GACAT2 levels were significantly increased in patients with GD (P<0.001) and preoperative patients with GC (P=0.040). Moreover, the individual relative changes of plasma GACAT2 expression following surgery were significantly associated with lymphatic metastasis (P=0.034), distal metastasis (P=0.035) and perineural invasion (P=0.039). Therefore, the results of the current study suggest that plasma-based GACAT2 may be developed as a tumor marker to screen and predict the prognosis of GC patients.

LncRNA-RMRP promotes carcinogenesis by acting as a miR-206 sponge and is used as a novel biomarker for gastric cancer.

Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis. However, the mechanisms of most lncRNAs in cancers are largely unknown. Because the RNA component of mitochondrial RNA processing endoribonuclease (RMRP) is one of the dysregulated lncRNAs in gastric cancer, this study explored its molecular mechanisms in carcinogenesis. RMRP levels in 792 tissues, plasma and gastric juices from patients with various stages of gastric tumorigenesis were analyzed by quantitative reverse transcription-polymerase chain reaction. Overexpression and RNA interference were used to manipulate RMRP expression by RMRP expression vector and small interfering RNAs, respectively. Its mechanisms were evaluated by flow cytometry, real-time cell analysis, plate colony formation assays, and xenograft models. RMRP levels in tissue, plasma and gastric juices from patients with gastric cancer were significantly different from those from controls. Its levels were significantly associated with Borrmann type and metastasis. Plasma and gastric juice RMRP had higher sensitivity and specificity than commonly used markers (such as carcinoembryonic antigen and carbohydrate antigen 19-9). Knockdown of RMRP significantly inhibited cell proliferation in vitro and in vivo, whereas overexpression of RMRP promoted cell growth. Acting as a miR-206 sponge, RMRP modulated cell cycle by regulating Cyclin D2 expression. RMRP plays a crucial role in gastric cancer occurrence and can be used as a novel biomarker for gastric cancer.