Objective:
We have already demonstrated that mesenchymal stem cells from patients with ankylosing spondylitis (ASMSCs) exhibited greater adipogenic differentiation potential than those from healthy ...donors (HDMSCs). Here, we further investigated the expression profile of long noncoding RNA (lncRNA) and mRNA, aiming to explore the underlying mechanism of abnormal adipogenic differentiation in ASMSCs.
Methods:
HDMSCs and ASMSCs were separately isolated and induced with adipogenic differentiation medium for 10 days. Thereafter, lncRNAs and mRNAs that were differentially expressed (DE) between HDMSCs and ASMSCs were identified
via
high-throughput sequencing and confirmed by quantitative real-time PCR (qRT–PCR) assays. Then, the DE genes were annotated and enriched by GO analysis. In addition, protein interaction network was constructed to evaluate the interactions between DE mRNAs and to find hub nodes and study cliques. Besides, co-expression network analysis was carried out to assess the co-expressions between DE mRNA and DE lncRNAs, and competing endogenous RNA (ceRNA) network analysis were conducted to predict the relationships among lncRNAs, mRNAs and miRNAs. The signaling pathways based on the DE genes and the predicted DE genes were enriched by KEGG analysis.
Results:
A total of 263 DE lncRNAs and 1376 DE mRNAs were found during adipogenesis in ASMSCs. qRT–PCR indicated that the expression of the top 20 mRNAs and the top 10 lncRNAs was consistent with the high-throughput sequencing data. Several lncRNAs (NR_125386.1, NR_046473.1 and NR_038937.1) and their target genes (SPN and OR1AIP2), together with the significantly co-expressed pairs of DE lncRNAs and DE mRNAs (SLC38A5-ENST00000429588.1, TMEM61-ENST00000400755.3 and C5orf46-ENST00000512300.1), were closely related to the enhanced adipogenesis of ASMSCs by modulating the PPAR signaling pathway.
Conclusion:
Our study analyzed the expression profiles of DE lncRNAs and DE mRNAs during adipogenesis in ASMSCs and HDMSCs. Several DE lncRNAs, DE mRNAs and signaling pathways that probably participate in the aberrant adipogenesis of ASMSCs were selected for future study. These results will likely provide potential targets for our intervention on fat metaplasia and subsequent new bone formation in patients with AS in the future.
The present study evaluated the clinical efficacy of chemotherapy in combination with cytokine-induced killer (CIK) biotherapy
compared to the chemotherapy alone. Fifty-nine advanced non-small cell ...lung cancer (NSCLC) patients were randomly divided
into two groups, group A (chemotherapy alone, including docetaxel 75 mg/m 2 , day 1; cisplatin, 25 mg/m 2 , days 1-4, tri-weekly) and group B (chemotherapy plus CIK cell transfusion). Autologous CIK cells were induced from the patients'
peripheral mononuclear cells in vitro and separated by cytometry and then transfused back the patients. The host cellular
immune function, clinical curative effects and quality of life (QOL) were examined and were compared between the two groups.
The host immune function was enhanced and QOL was improved in the patients treated by chemotherapy plus CIK biotherapy compared
to the patients treated by chemotherapy alone. The overall response rate (ORR) was 43.3% and 44.8% in groups A and B, respectively.
The disease control rate (DCR) was higher in group B than in group A (89.7% vs. 65.5%, p=0.030). The time to progression was
4.67 months (95% CI 3.98-6.02 months) in group A and 6.65 months (95% CI 4.70-7.30 months) in group B and the median survival
time was 11.0 months (95% CI 7.88-14.1 months) in group A and 15.0 months (95% CI 11.04-18.96 months) in group B. Compared
to patients in group A, the patients in group B had significantly longer progression-free survival (p=0.042) and overall survival
(p=0.029). No severe side-effects occurred in the CIK cell transfusion patients. It was concluded that chemotherapy plus CIK
cells has potential benefits compared to chemotherapy alone in patients suffering from advanced NSCLC and autologous CIK cell
transfusion has no obvious side-effects.
Tissue-resident CD8
T cells (CD103
CD8
T cells) are the essential effector cell population of anti-tumor immune response in tissue regional immunity. And we have reported that IL-33 can promote the ...proliferation and effector function of tissue-resident CD103
CD8
T cells. As of now, the immunolocalization and the prognostic values of tissue-resident CD8
T cells in human hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) still remain to be illustrated.
In our present study, we used the tissue microarrays of HCC and ICC, the multicolor immunohistochemistry (mIHC), and imaging analysis to characterize the tissue-resident CD8
T cells in HCC and ICC tissues. The prognostic values and clinical associations were also analyzed. We also studied the biological functions and the cell-cell communication between tumor-infiltrating CD103
CD8
T cells and other cell types in HCC and ICC based on the published single-cell RNA sequencing (scRNA-seq) data.
Our work unveiled the expressions of CD8 and CD103 and immunolocalization of tissue-resident CD8
T cells in human HCC and ICC. Elevated CD8
T cells indicated a better overall survival (OS) rate, implying that tumor-infiltrating CD8
T cells in HCC and ICC could serve as an independent prognostic factor. Moreover, the number of CD103
CD8
T cells was increased in HCC and ICC tissues compared with adjacent normal tissues. HCC patients defined as CD8
CD103
had a better OS, and the CD8
CD103
group tended to have a poorer prognosis in ICC. Evaluation of the CD103
CD8
T-cell ratio in CD8
T cells could also be a prognostic predictor for HCC and ICC patients. A higher ratio of CD103
CD8
T cells over total CD8
T cells in HCC tissues was negatively and significantly associated with the advanced pathological stage. The percentage of higher numbers of CD103
CD8
T cells in ICC tissues was negatively and significantly associated with the advanced pathological stage. In contrast, the higher ratio of CD103
CD8
T cells over total CD8
T cells in ICC tissues was negatively and significantly associated with the advanced pathological stage. In addition, single-cell transcriptomics revealed that CD103
CD8
T cells were enriched in genes associated with T-cell activation, proliferation, cytokine function, and T-cell exhaustion.
The CD103
tumor-specific T cells signified an important prognostic marker with improved OS, and the evaluation of the tissue-resident CD103
CD8
T cells might be helpful in assessing the on-treatment response of liver cancer.
Recently, the use of chimeric antigen receptor-modified T (CAR-T)-cells in the treatment of hematological tumors has been successful and has become a clinical hotspot in tumor immunotherapy. However, ...their wide application is limited by inherent risks such as graft-versus-host disease (GvHD) and the amount of time it takes to produce CAR-T cells. Natural killer (NK) cells can be xenografted and have the potential to become off-the-shelf products, making CAR-NK cell therapies universal products. These products may be safer than CAR-T cell therapy. Considering that the fundamental researche is still in its infancy, this review focuses on clinical achievements and new strategies for improving the safety and efficacy of CAR-NK cell therapy, as well as the corresponding challenges.
•Targeted lysis of CAR-NK is based on CAR and receptor dependent mechanisms.•Achievements of CAR-NK are described in detail in pre-clinical and clinical studies.•Introducing IL15, ICR and suicide genes into CAR-NK enhance its safety and efficacy.•Advances of CAR-NK will lead tumor immunotherapy into the era of precision medicine.
The occurrence of early esophageal cancer located within an area of leiomyoma is extremely rare, and its clinical features and treatment methods have not been well described. We herein report the ...clinical characteristics, diagnosis, and treatment methods of early esophageal cancer that developed on top of a leiomyoma in the upper third of the esophagus in a 78-year-old woman. All tumor marker concentrations were normal. The leiomyoma was correctly diagnosed as a submucosal tumor by endoscopy and endoscopic ultrasonography. Endoscopic biopsy revealed esophageal squamous cell carcinoma. Both lesions were successfully treated by endoscopic submucosal dissection. The patient was followed up for 6 months without recurrence. Endoscopic submucosal dissection was a successful initial treatment method for esophageal carcinoma coexisting with esophageal leiomyoma in this case.
Microwave ablation (MWA) is a recently developed thermal ablation technique that has been used for the treatment of different types of tumours. In the present study, we retrospectively evaluated the ...safety and efficacy of CT-guided percutaneous MWA for the treatment of colorectal cancer (CRC) pulmonary metastases.
From June 2010 to June 2015, 48 unresectable lesions in 32 patients with CRC pulmonary metastases were subjected to CT-guided MWA. Imaging follow-up was with contrast-enhanced CT and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT.
Oncologic imaging showed that 42 (87.5%) of the 48 lesions in the 32 patients were completely ablated. Needle track metastatic seeding was not found, and no patient deaths occurred within 30 d after ablation. The mean hospital stay was 3 d (range, 2-7 d). Pneumothorax was the most frequent complication and occurred in 6 (12.5%) of the 48 lesions. The median survival time was 31 months (95% CI: 15.4-46.6). The 1-, 2- and 3-year survival rates were 79.5%, 63.1% and 44.4%, respectively. Univariate Cox regression analysis showed that tumour size, disease-free interval (DFI) and number of tumours were significantly related to the overall survival time (p = .007, p = .022 and p = .030, respectively). Multivariate analysis showed that tumour size was an independent prognostic factor for survival (p = .017).
CT-guided percutaneous MWA is a safe and effective minimally invasive method for treating CRC pulmonary metastases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Retinoic acid-induced protein I (RIG-I), known as a cytoplastic pattern recognition receptor, can recognize exogenous viral RNAs, and then initiate immune response. Recently, numerous studies also ...showed that RIG-I play an important role in oncogenesis and cancer progression as well. As of now, the expression pattern and the role of RIG-I in gastric cancer still remain largely unexplored. In this study, we investigated the clinical associations of RIG-I expression in human gastric cancer tissues and further explore its important contribution in the regulation of malignant phenotype of gastric cancer cells.
Immunohistochemistry was performed to study the correlation between patients' clinical parameters and RIG-I expression in gastric cancer tissues. Knockdown of RIG-I was achieved by RNAi technology to examine the contribution of RIG-I in the regulation of biological functions in the cell lines of human gastric cancer. The Affymetrix GeneChip was performed to figure out the differential gene expression profile between RIG-I wild type and RIG-I knockdown cell lines of gastric cancer.
Immunohistochemistry result demonstrated that the expression of RIG-I in gastric cancer tissues significantly correlated with pathological stage and patients' prognoses. Furthermore, decreased RIG-I expression in human gastric cancer cell lines could significantly increase the cell migration, cell viability, and the ratio of cells in G2/M phase. Our microarray analysis also revealed that the differentially expressed gene profiles were enriched in related signal pathways or biological processes in KEGG or GO analysis respectively.
Our present findings showed that the decreased RIG-I expression significantly correlated with patients' prognoses, and such down-regulation could promote the cell invasion in this malignancy.
Androgen deprivation therapy is the mainstay of treatment of advanced prostate cancer (PCa). However, a significant portion of patients experience disease relapse and tumors ultimately evolve into ...castration resistant prostate cancer (CRPC), for which there is no cure in the clinic. The Polycomb protein enhancer of zeste homolog 2 (EZH2) is frequently overexpressed in CRPC. It is unclear whether EZH2 can be a therapeutic target in CRPC. Here, we demonstrated that chemo- and radiotherapy agents such as camptothecin (CPT) and γ irradiation decrease EZH2 expression in various PCa cell lines. We provided evidence that functional p53 and RB proteins are required for CPT- and irradiation-induced downregulation of EZH2 in CRPC cells. We demonstrated that EZH2-specific small molecule inhibitors mitigate CRPC cell growth. We further showed that the EZH2 inhibitor GSK126 inhibits both Polycomb-dependent and -independent functions of EZH2 in PCa cells. Importantly, we found that inhibition of EZH2 by genetic and pharmacological means sensitizes CRPC cells to CPT-induced apoptotic death and growth inhibition in culture and in mice. Our data suggest that concomitant administration of small molecule inhibitors of EZH2 may significantly increase the anti-tumor efficacy of conventional chemo- and radiotherapies in CRPC.
To establish the prognostic value of B7-H4 expression by tumor cells in gastric cancer patients, we evaluated the association of B7-H4 expression with clinicopathologic factors and overall survival ...of gastric cancer patients. A retrospective cohort study including 156 gastric cancer patients was performed in the present report. Immunohistochemical assay was used to evaluate the expression of B7-H4 in the surgical specimens of gastric cancer tissues. Multi-univariate COX model was then used to evaluate the association of B7-H4 expression with the patients’ survival and clinicopathological parameters. B7-H4 expression in the gastric cancer cells was observed in about 44.9% gastric cancer specimens. Univariate analysis demonstrated that there was no correlation between B7-H4 expression and sex, age, histological type, pathological grade or tumor size. In contrast, B7-H4 expression correlated positively with cancer invasiveness and lymph node metastasis. In addition, the median overall survival time of patients with lower B7-H4 expression was 13 months longer than that of patients with higher expression (χ
2
= 12.38,
P
< 0.0001), and the median disease-free survival time of patients with lower B7-H4 expression was significantly longer than that of patients with higher expression (33 vs. 16 months, χ
2
= 14.977,
P
< 0.0001). After adjustment for other confounding factors, the COX model analysis indicated that the death risk was significantly higher in patients with higher B7-H4 expression than those with lower expression (RR = 1.85, 95% CI = 1.15–2.96). The present study demonstrated that higher B7-H4 expression in cancer cells was associated with poor prognosis of gastric cancer patients. This is consistent with the idea that B7-H4 promotes cancer progression, likely via inhibition of anti-tumor immune responses.
Long non-coding RNAs (lncRNAs) play important roles in various biological processes and human diseases, including cancer. In this study, we demonstrated a regulatory relationship between lncRNA ...GRIK1-AS1 and miR-375/IFIT2 axis in gastric cancer. Our results show a decreased expression of GRIK1-AS1 in gastric cancer tissues compared to adjacent normal gastric tissues. Gastric cell lines also have reduced levels of GRIK1-AS1 compared to gastric epithelial cell line GES-1. Ectopic expression of GRIK1-AS1 in gastric cancer cell lines significantly inhibits cellular viability, migration, and invasion. RNA-pull down and the luciferase activity assays show that GRIK1-AS1 mainly interacts specifically with miR-375. We further demonstrate a negatively regulatory relationship between lncRNA GRIK1-AS1 and miR-375. We discovered that IFIT2 was one of the direct key downstream target genes of miR-375, and established the important role of the GRIK1-AS1/miR-375/IFIT2 axis in the progression of gastric cancer. Taken together, our results revealed a novel mechanism of GRIK1-AS1 as a sponge to miR-375 that impacts gastric cancer progression
via
modulating target mRNA IFIT2 translation, and as a result, opens a new strategy to future GRIK1-AS1 based therapeutic development.
PDF
