Colon cancer is the third most common cancer and the second leading cause of cancer‐related death worldwide. Dysregulated RNA splicing factors have been reported to be associated with tumorigenesis ...and development in colon cancer. In this study, we interrogated clinical and RNA expression data of colon cancer patients from The Cancer Genome Atlas (TCGA) dataset and the Gene Expression Omnibus (GEO) database. Genes regulating RNA splicing correlated with survival in colon cancer were identified and a risk score model was constructed using Cox regression analyses. In the risk model, RNA splicing factor peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PPARGC1) is correlated with a good survival outcome, whereas Cdc2‐like kinase 1(CLK1), CLK2, and A‐kinase anchor protein 8‐like (AKAP8L) with a bad survival outcome. The risk model has a good performance for clinical prognostic prediction both in the TCGA cohort and the other two validation cohorts. In the tumor microenvironment (TME) analysis, the immune score was higher in the low‐risk group, and TME‐related pathway gene expression was also higher in low‐risk group. We further verified the mRNA and protein expression levels of these four genes in the adjacent nontumor, tumor, and liver metastasis tissues of colon cancer patients, which were consistent with bioinformatics analysis. In addition, knockdown of AKAP8L can suppress the proliferation and migration of colon cancer cells. Animal studies have also shown that AKAP8L knockdown can inhibit tumor growth in colon cancer in vivo. We established a prognostic risk model for colon cancer based on genes related to RNA splicing regulation and uncovered the role of AKAP8L in promoting colon cancer progression.
we interrogated transcriptome and the corresponding clinical data of colon cancer patients from the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset to investigate prognosis associated splicing‐related signature.And our study established a prognostic risk model based on RNA splicing regulation related genes for colon cancer.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
According to the EPOC study, chemotherapy could improve 5-year disease-free survival of stage IV colon cancer patients by 8.1%. However, more molecular biomarkers are required to identify patients ...who need neoadjuvant chemotherapy. DENND2D expression was evaluated by immunohistochemistry in 181 stage IV colon cancer patients. The prognosis was better for patients with DENND2D expression than patients without DENND2D expression (5-year overall survival OS: 42% vs. 12%, p = 0.038; 5-year disease-free survival: 20% vs. 10%, p = 0.001). Subgroup analysis of the DENND2D-negative group showed that patients treated with neoadjuvant chemotherapy achieved longer OS than patients without neoadjuvant chemotherapy (RR = 0.179; 95% CI = 0.054-0.598; p = 0.003). DENND2D suppressed CRC proliferation in vitro and in vivo. Downregulation of DENND2D also promoted metastasis to distant organs in vivo. Mechanistically, DENND2D suppressed the MAPK pathway in CRC. Colon cancer patients who were DENND2D negative always showed a worse prognosis and were more likely to benefit from neoadjuvant chemotherapy. DENND2D may be a new prognostic factor and a predictor of the need for neoadjuvant chemotherapy in stage IV colon cancer.
To conduct a meta-analysis of the effectiveness and safety of
(TwHF) extracts for the treatment of rheumatoid arthritis (RA).
A systematic literature search was conducted in PubMed, EMBASE, Cochrane, ...Medline, CNKI, SinoMed and WanFang Library till 12 July 2017. All included studies were analyzed with the use of the Review Manager 5.2 software according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement protocol.
Fourteen randomized controlled trials (RCTs) were identified. TwHF extracts provided a statistically significant improvement in grip strength (GS), swelling joint count (SJC) and morning stiffness (MS) compared with placebo (
< 0.001). The meta-analysis showed significant differences between TwHF extract-treated group and the DMARDs group in GS, MS, C-reactive protein (CRP), and tender joint count (TJC) (
< 0.05), aside from ESR and SJC (
> 0.05). The pooled results also displayed significant differences between the combination of TwHF extracts with DMARDs and the DMARDs alone group in ESR, CRP, SJC, and TJC (
≤ 0.05). For the safety analysis, two trials favored TwHF extract-treatment and one trial favored non-TWHF extract-treatment in AEs (
< 0.05). Eleven trials showed no statistically significant differences between TwHF extract-treated group and the DMARDs group (
> 0.05).
The findings of this systematic review with meta-analysis indicate that TwHF extracts provides statistically significant and clinically important improvement in RA symptoms and has an acceptable safety profile.
Magnetoelectric composites enjoy large magnetoelectric transfer efficiency at resonance frequency, accompanying a large phase shift. We prepared two magnetoelectric laminate composites to research ...the origin of large phase shift and magnetoelectric characteristics by electric-field-induced strain and magnetic-field-induced strain. The piezoelectric part plays a dominant role in both the direct and converse magnetoelectric resonances. The electromechanical resonance inspires direct and converse magnetoelectric resonant peaks, and results in the magnetoelectric phase shift of near π around the resonance frequency. However, the magnetostrictive part is difficult to inspire the magnetoelectric resonance and phase shift.
Whether primary tumor location (PTL) is predictive of survival benefits following primary tumor resection plus metastasectomy (PMTR) and primary tumor resection (PTR) alone in stage IV colorectal ...cancer patients is not known. We sought to address this issue by employing instrumental variable analysis to evaluate the efficacy of PMTR and PTR with stratification for primary tumor location in stage IV colorectal cancer patients.
Stage IV colorectal cancer patients diagnosed between January 1, 2005 and December 31, 2015 were identified from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. To account for both measured and unmeasured confounders, the efficacy of PMTR and PTR in the left- and right-sided subgroups was evaluated using instrumental variable analysis, with the health service area as the instrument variable. Overall survival (OS) was the primary outcome of interest.
A total of 50,333 eligible patients were analyzed (left-sided, n = 29,402 and right-sided, n = 20,931). OS was significantly better with PMTR than with other treatments (PTR, metastasectomy only, or no surgery) in patients with left-sided tumors (hazard ratio HR = 0.37 95% CI 0.24-0.58, P < 0.001), but not in patients with right-sided tumors (HR = 0.98 95% CI 0.65-1.47, P = 0.910; interaction test P < 0.001). OS was comparable in patients treated with PTR and those treated with no surgery in both the left-sided (HR = 1.11 95% CI 0.68-1.81, P = 0.690) and right-sided (HR = 0.85 95% CI 0.50-1.43, P = 0.530; interaction test P = 0.466) subgroups.
PMTR appears to only benefit patients with left-sided stage IV colorectal cancer but not those with right-sided tumors. PTR does not improve OS, regardless of primary tumor location. When selecting patients for PMTR, primary tumor location should be considered. Overuse of PTR should be avoided.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
This study aimed to investigate the potential factors associated with adherence to colonoscopy among participants who were preliminarily screened positive in a community‐based colorectal ...cancer screening program in China.
Methods
This study analyzed data from 1219 out of 6971 community residents who were identified as positive cases by the well‐validated high‐risk factor questionnaire (HRFQ) or fecal immunochemical test (FIT) in the preliminary screening stage for colorectal neoplasms. Patients showing adherence to colonoscopy were defined as those who received positive results in a preliminary screening for colorectal neoplasms and later received a colonoscopy examination as required. The associations of social‐demographic factors, lifestyle behaviors, history of diabetes, body mass index (BMI), and risk factors in the HRFQ with adherence to colonoscopy were evaluated using logistic regression models.
Results
Among 1219 participants who preliminarily screened positive, the top five risk factors reported by the participants were chronic constipation (25.9%), hematochezia (23.5%), family history of CRC in first‐degree relatives (22.1%), chronic diarrhea (21.8%), and history of polyps (16.6%). Around 14.2% of participants who preliminarily screened positive reported three or more risk factors, and the proportion was 26.2% among participants who were positive according to both HRFQ and FIT. Among all participants who were preliminarily screened positive, the multivariable results showed that those who were married (OR = 1.58, 95% CI: 1.12, 2.25, p = 0.01), had chronic diarrhea (OR = 1.34, 95% CI: 1.00, 1.78, p = 0.047), and had a positive FIT (OR = 1.60, 95% CI: 1.21, 2.10, p < 0.001 for patients who were negative according to HRFQ but positive according to FIT; OR = 2.12, 95% CI: 1.33, 2.78, p = 0.002 for patients who were positive for both HRFQ and FIT) were more likely to adhere to colonoscopy, while participants with a history of cancer (OR: 0.50, 95% CI: 0.31, 0.79, p = 0.003) were less likely to adhere to colonoscopy. The results among participants who were tested positive according to only HRFQ were similar to those among all participants who were tested positive according to HRFQ or FIT. However, among participants who were tested positive according to only FIT, we only found that those who were married (OR = 2.52, 95% CI: 1.08, 5.90, p = 0.033) had a higher odds of adhering to colonoscopy, while those with a history of diabetes (OR = 0.35, 95% CI: 0.13, 0.96, p = 0.042) were less likely to adhere to colonoscopy.
Conclusion
Our findings provide evidence supporting the development of tailored interventional strategies that aim to improve adherence to colonoscopy for individuals with a high risk of colorectal neoplasms. Both barriers and facilitators associated with adherence to colonoscopy should be considered in supportive systems and health policies. However, further well‐designed prospective studies are warranted to confirm our findings.
For the participation rate of colonoscopy screening is still disappointingly low in China. We find out the factors associated with colonoscopy adherence among individuals who were positive in the preliminary screening for colorectal neoplasms.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Prior reports have indicated that defective mismatch repair (MMR) has a favorable impact on outcome in colorectal cancer patients treated with surgery, immunotherapy, or adjuvant chemotherapy. ...However, the impact of MMR status on response to neoadjuvant radiotherapy in rectal cancer is not well understood. Here we report that dMMR was associated with improved disease-free survival (DFS) (
= 0.034) in patients receiving neoadjuvant chemotherapy (NCT). Patients with dMMR tumors who received neoadjuvant chemoradiotherapy (NCRT) achieved significantly worse DFS (
= 0.026) than those treated with NCT. Conversely, NCRT improved DFS (
= 0.043) in patients with pMMR tumors, especially for stage III disease with improved DFS (
= 0.02). The presence of dMMR was associated with better prognosis in rectal cancer patients treated with NCT. NCT benefited patients with dMMR tumors; while NCRT benefited patients with stage III disease and pMMR tumors. Patients stratified by MMR status may provide a more tailored approach to rectal cancer neoadjuvant therapy.
The present study was aimed to investigate the effect of dihydroartemisinin on the colon cancer cell proliferation and apoptosis. The results from MTT assay revealed a concentration and time ...dependent relation between the inhibition of SW 948 cell viability and dihydroartemisinin addition. The viability of SW 948 cells was reduced to 45 and 24% on treatment with 30 and 50µM, respectively concentrations of dihydroartemisinin after 48h. Morphological examination of SW 948 cells showed attainment of rounded shape and cluster formation on treatment with dihydroartemisinin. Western blot analysis showed a significant increase in the activation of caspase-3 and expression of cleaved PARP by dihydroartemisinin treatment. The activation of PPARγ was increased significantly in SW 948 cells by treatment with dihydroartemisinin. Compared to control, the migration potential of SW 948 cells was reduced significantly (p<0.005) and the expression levels of MMP-2 and -9 inhibited by dihydroartemisinin at 50µM concentration. In the dihydroartemisinin treatment group colon tumor formation was significantly inhibited on treatment with 20mg/kg doses of dihydroartemisinin after 30days. Therefore, dihydroartemisinin inhibits colon cancer growth by inducing apoptosis and increasing the expression of PPARγ. Thus dihydroartemisinin can be used for the treatment of colon cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Taking Ta–W alloy system as an example, the concentration formulae of alloy genes of DO
3
-type alloys in BCC structures were derived on the basis of the theory of alloy genes and the number of ...coordination atoms. The concentrations of alloy genes of DO
3
-TaW
3
and DO
3
-Ta
3
W ordered alloys were calculated as functions of composition xW and ordering degree (s). When s=smax, the concentrations of alloy genes of stoichiometric DO
3
-TaW
3
compound are equal to those of alloys, that is,
x
8
Ta
0.25(at),
x
4
W
0.5(at),
x
8
W
0.25(at). The concentrations of alloy genes of stoichiometric DO
3
-Ta
3
W compound are also equal to those of alloys, that is,
x
0
Ta
0.25(at),
x
4
Ta
0.5(at),
x
0
W
0.5(at). As ordering degree decreases, alloy genes of DO
3
-TaW
3
and DO
3
-Ta
3
W ordered alloys will split. And the degree of splitting of alloy genes increases with the ordering degree decreasing. The atomic states and properties of DO
3
-TaW
3
and DO
3
-Ta
3
W ordered alloys were calculated as a function of composition xW. The reason was pointed out that preparation of DO
3
-TaW
3
and DO
3
-Ta
3
W intermetallic compounds is difficult due to small differences in their cohesive energies. It will provide theoretical guidance for the scientific designation to new candidate for ultrahigh- temperature materials in areo-engine applications.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Increased expression of programmed death-ligand 1 (PD-L1) on tumor cells can be found in various malignancies; however, very limited information is known about its role in anal squamous cell ...carcinoma (ASCC). This study explored PD-L1 expression in ASCC patients and its association with patients' clinicopathological features, CD8+ T cell infiltration, and prognosis.
Formalin-fixed paraffin-embedded tumor samples from 26 patients with ASCC were retrieved. The levels of PD-L1 expression on the membrane of both tumor cells and tumor-infiltrating mononuclear cells (TIMCs) were evaluated by immunohistochemistry. CD8+ T cell densities, both within tumors and at the tumor-stromal interface, were also analyzed. Baseline clinicopathological characteristics, human papilloma virus (HPV) status, and outcome data correlated with PD-L1-positive staining.
PD-L1 expression on tumor cells and TIMCs was observed in 46% and 50% of patients, respectively. Nineteen patients (73%) were HPV positive, with 7 showing PD-L1-positive staining on tumor cells and 9 showing PD-L1-positive staining on TIMCs. Increasing CD8+ density within tumors, but not immune stroma, was significantly associated with decreased PD-L1 expression by both tumor cells and TIMCs (
=0.0043 and
=0.0007). Patients with negative PD-L1 expression had significantly better progression-free survival (
=0.038 and
=0.0443) and a non-statistically significant trend toward longer overall survival (
=0.0882 and
=0.1222) compared with patients with positive PD-L1 expression.
PD-L1 is widely expressed on the membrane of tumor cells and TIMCs in ASCCs. Its negative impact on prognosis may be due to the diminished CD8+ T cell infiltration within tumors.
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