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Aim. The aim of our work was to determine the utility of DNM1 as a biomarker for the diagnosis and prognosis of colon cancer (CC). Methods. DNM1 expression variations in CC vs. normal tissues were investigated using The Cancer Genome Atlas (TCGA) database. The association of DNM1 expression levels with the clinicopathological variables in CC prognosis was investigated using logistic regression analyses. Independent prognostic factors for CC were evaluated using univariate and multivariate Cox regression analyses. The correlation between DNM1 expression and immune cell infiltration was estimated using single-sample Gene Set Enrichment Analysis (ssGSEA). Results. DNM1 expression in CC tissues was significantly higher than that in normal tissues. High DNM1 expression was significantly correlated with M stage, N stage, perineural invasion and lymphatic invasion and predicted poor prognosis. The univariate analysis highlighted that DNM1 was an independent CC risk factor. Results of ssGSEA showed that DNM1 was linked to several cancer-related pathways, including the neuroactive ligand-receptor interaction, hypertrophic cardiomyopathy, ECM-receptor interaction, dilated cardiomyopathy, and calcium signaling pathway. Moreover, DNM1 expression was positively correlated with the level of infiltration by Neutrophils, Tregs, NK cells, and Macrophages. Conclusion. DNM1 has a significant function and has diagnostic and prognostic potential for CC. [ABSTRACT FROM AUTHOR]

Dysregulated long noncoding RNAs (lncRNAs) remains to be explored in tumorigenesis. LncRNA HOXC13 antisense RNA (HOXC13‐AS) has been found as an oncogene in many cancers; however, the role of HOXC13‐AS in breast cancer still elusive. In this study, the HOXC13‐AS levels and its role in cell proliferation was first measured by real‐time quantitative polymerase chain reaction, Cell Counting Kit‐8 assay, and colony formation assay. It showed that HOXC13‐AS was increased in breast cancer tissues compared with the adjacent normal tissues and upregulated HOXC13‐AS promoted the growth of breast cancer cells. Then, we found that the miR‐497‐5p levels were downregulated in cancer tissues compared with the adjacent tissues and miR‐497‐5p suppressed breast cancer cell proliferation. Further study showed that HOXC13‐AS could function as a "sponge" for miR‐497‐5p then suppress miR‐497‐5p expression. Moreover, we next identified that Phosphatase and Tensin homolog (PTEN) is the target of miR‐497‐5p. Overexpression of miR‐497‐5p by chemical mimics decreased the expression of PTEN, while downregulation of miR‐497‐5p by HOXC13‐AS rescued the expression of PTEN. Finally, we showed that HOXC13‐AS promoted the proliferation of breast cancer cells and tumor growth through miR‐497‐5p/PTEN axis in vitro and in vivo. Hence, we conclude that HOXC13‐AS, which is significantly upregulated in breast cancers, promoted cell proliferation through the suppressed miR‐497‐5p and further upregulated PTEN. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety profile of combining vandetanib with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Methods: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ASCO Abstracts, ESMO Abstracts, Wanfang Database, CNKI were searched. Eligible studies were the randomized clinical trials (RCTs) that compared the efficacy and safety profile of adding vandetanib to chemotherapy with single chemotherapy in patients with advanced NSCLC. The outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicities. All meta-analysis were performed using Review Manager 5.1. The fixed-effect model weighted by the Mantel-Haenszel method was used. When considerable heterogeneity was found (p<0.1, or I2>50%), further analysis (subgroup analysis, sensitivity analysis or random-effect model) was performed to identify potential cause. Results: Results reported from 5 RCTs involving 2284 patients were included in the analysis. Compared to chemotherapy alone, the addition of vandetanib resulted in a significant longer PFS (HR 0.79 [0.72–0.87], p<0.00001) and a higher ORR (RR 1.75 [1.43–2.15], p<0.00001), but failed to show advantage on OS (HR 0.96 [0.87–1.06], p = 0.44). Conclusion: Vandetanib has activity in NSCLC. Identification of predictive biomarkers is warranted in future trials to select a subset of patients with advanced NSCLC who may benefit from vandetanib. [ABSTRACT FROM AUTHOR]

This study intended to prepare liver-targeting solid lipid nanoparticles (SLNs) with a hepatoprotective drug, cucurbitacin B (Cuc B), using a galactosylated lipid, N-hexadecyl lactobionamide (N-HLBA). The galactosyl-lipid N-HLBA was prepared via the lactone form intermediates of lactobionic acid and synthesized by anchoring galactose to hexadecylamine lipid. The Cuc B-loaded galactosylated and conventional SLNs were successfully prepared by a high-pressure homogenization method. The two SLNs showed similar physical and pharmaceutical properties, including: the particle size measured by laser diffraction was 135 nm for galactosylated SLN (GalSLN) and 123 nm for conventional SLNs (CSLN); zeta potentials were −31.6 mV (GalSLN) and −34.3 mV(CSLN); in vitro release behavior of the two SLNs was similar, and both showed the biphasic drug release pattern with burst release at the initial stage and prolonged release afterwards. In contrast, the two SLNs demonstrated a marked difference in in vitro cellular cytotoxicity and in vivo tissue distribution performances. The IC50 values of Cuc B in the two SLNs were by far lower than those of Cuc B solution and further Cuc B-GalSLN had about half the IC50 value of Cuc B-CSLN. These results indicated that the encapsulation of Cuc B in SLNs resulted in the enhancement of cytotoxic activity, and galactosyl ligand could further enhance the cellular accumulation and cytotoxicity of Cuc B. The weighted-average overall drug targeting efficiency (Te) was used to evaluate the liver targetability. Cuc B-GalSLN gave a relatively high (Te)liver value of 63.6%, ∼ 2.5-times greater than that of Cuc B-CSLN (25.3%) and Cuc B solution (23.8%). In summary, the incorporation of N-HLBA into SLNs significantly enhanced the liver targetability of Cuc B-loaded SLNs and GalSLN had a great potential as a drug delivery carrier for improved liver targetability. [ABSTRACT FROM AUTHOR]

S100A4 plays important roles in tumor development and metastasis, but its role in regulating inflammation and colitis-associated tumorigenesis has not been well characterized. Here, we report that S100A4 expression was increased in azoxymethane (AOM) and dextran sulfate sodium (DSS) induced colorectal cancer (CRC) in mice. After AOM/DSS treatment, both S100A4-TK mice with the selective depletion of S100A4-expressing cells and S100A4-deficient (S100A4−/−) mice developed fewer and smaller tumors than wild-type (WT) control littermates. Furthermore, S100A4−/− mice were resistant to DSS-induced colitis, reduced infiltration of macrophages, and the diminished production of proinflammatory cytokines. Further studies revealed that reduced colon inflammation and colorectal tumor development in S100A4−/− mice were partly due to the dampening of nuclear factor (NF)-κB activation in macrophages. Furthermore, the administration of a neutralizing S100A4 antibody to WT mice significantly decreased AOM/DSS-induced colon inflammation and tumorigenesis. These results indicate that S100A4 amplifies an inflammatory microenvironment that promotes colon tumorigenesis and provides a promising therapeutic strategy for treatment of inflammatory bowel disease and prevention of colitis-associated colorectal carcinogenesis. [ABSTRACT FROM AUTHOR]

Objectives The purpose of this study was to explore the role of single nucleotide polymorphisms (SNPs) in cytokine signaling genes and to compare them with clinical outcomes in surgical patients with non–small cell lung cancer (NSCLC). Methods SNPs of the cytokine signaling pathway were analyzed using peripheral blood of 722 patients who underwent resection of stage I to III NSCLC between 1995 and 2009. Cox proportional hazard analyses were performed to identify SNPs associated with overall survival (OS) and risk of recurrence. Internal validation using bootstrap analysis selected SNPs for unfavorable genotype and survival tree analysis. Results Seventeen and 9 SNPs were independently associated with OS and recurrence, respectively. Patients with ≥9 unfavorable genotypes experienced worse OS (median, 41 months) than patients with 7 to 8 (89 months) and ≤6 (153 months) after median follow-up of 71 months ( P = 2.86 × 10 −23 ). Patients with ≤3 unfavorable genotypes had greater time to recurrence (median not reached) than those with 4 to 6 (114 months) and ≥7 (44 months; P = 1.3 × 10 −5 ). Survival tree analysis classified patients into 3 risk groups. Patients in the intermediate- (median OS, 82 months) and high-risk groups (43 months) had worse survival than the low-risk group (176 months; P = 5.51 × 10 −20 ). Median time to recurrence was worse in the intermediate- (114 months) and high-risk groups (58 months) than the low-risk group (median not reached; P = 2.52 × 10 −9 ). Conclusions Genetic variants in cytokine signaling pathways were associated with clinical outcomes in NSCLC patients treated with surgery individually and cumulatively. Further studies are necessary to elucidate our findings and translate them into the clinical setting. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer remains a major health issue and a leading cause of death worldwide. This study presented a long-term survival data of gastric cancer registered in Shanghai of China from 1972-2003, with aims to describe the trends as well as the age, sex, stage and tumor sites specific characteristics.Methods: The main source of information on cancer cases was the notification card sending to the registry. The residential status of cancer cases was confirmed by home-visits. The methods of follow-up have been a mixture of both active and passive ones.Results: We observed an increased trend of survival probability during the last decades. Patients diagnosed during 1972-1976 had a 5-years relative survival rate at 12% for males and 11% for females, respectively, which had dramatically increased to 30% for male and 32% for female patients respectively during the period of 2002-2003. Among the patients diagnosed in 2002-2003, the overall survival probability declined with patient's age at the time of diagnosis. The lowest survival rate was observed among the oldest group, with the median survival time of 0.8 years. Patients diagnosed with stage I had a higher relative survival rate. Patients with cardia cancer had the worst prognosis, with the 5-year relative survival rate of 29%.Conclusions: The survival probability of patients with gastric cancer in Shanghai has improved significantly during the last decades. Age, stage and site of tumor have an impact on prognosis. [ABSTRACT FROM AUTHOR]

Abstract: Glycosylation is a widespread modification of plant secondary metabolites, and catalyzed by a superfamily of enzymes called UDP-glycosyltransferases (UGTs). UGTs are often involved in late biosynthetic steps and show broad substrate specificity or regioselectivity. In this study, the acceptor promiscuity of a Rosa hybrid UGT RhGT1 and an evolved microbial UGT OleDPSA toward a small flavonoid library was probed and compared. Interestingly, RhGT1 showed comparable acceptor promiscuity in comparison with OleDPSA, though the acceptor binding pocket of the latter is much more open and large. This clearly indicates that stabilization of the acceptor position by suitable hydrophobic interactions is important for the specificity or regioselectivity determination as well as overall fit of the acceptor into a ‘big enough’ binding pocket. This also poses a challenge for structure-based UGT engineering to alter the glucosylation pattern of flavonoids. [Copyright &y& Elsevier]

The signal adaptor MyD88, an essential component of TLR signaling, plays an important role in gut-microbiome interactions. However, its contribution to colitis-associated cancer (CAC) is still controversial. Far less is known about the specific effects of MyD88 signaling in myofibroblasts in CAC development. Here, we used a CAC mouse model in which MyD88 was selectively depleted in myofibroblasts. Myofibroblast MyD88-deficient mice are resistant to azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced tumorigenesis, as evidenced by the decrease in the number and sizes of tumors. MyD88 deficiency in myofibroblasts attenuates intestinal epithelial cell (IEC) proliferation after acute DSS-induced colitis. Furthermore, MyD88 signaling in myofibroblasts increases the secretion of osteopontin (OPN), which promotes macrophage M2 polarization through binding to α v β 3 and CD44, leading to activation of the STAT3/PPARγ pathway. Thus, MyD88 signaling in myofibroblasts crucially contributes to colorectal cancer development and provides a promising therapeutic target for the prevention of colitis-associated carcinogenesis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Recent advances in T cell-related immunotherapy have brought remarkable progress in the treatment of non-small cell lung cancer (NSCLC). However, whether and how genetic variations of T cell cancer immune response genes can influence clinical outcomes of NSCLC patients remain obscure., Methods: In this multiphase study, we assessed 2450 single-nucleotide polymorphisms (SNPs) from 280 T cell cancer immune response-related genes in 941 early-stage NSCLC patients (discovery n=536; validation n=405) to analyze the variants' associations with outcomes and to observe the effects on T cell phenotypes., Results: We found 14 SNPs in 10 genes were associated with NSCLC outcomes (p<0.05) in both phases. Among them, TRB :rs1964986 was the most significant variant associated with recurrence risk after meta-analysis (HR 1.84, 95% CI 1.35 to 2.52, p=1.15E-04), while IDO1 :rs10108662 was the most significant SNP associated with death risk (HR 1.87, 95% CI 1.40 to 2.51, p=2.17E-05). Analysis of unfavorable genotypes indicated cumulative effects on death and recurrence risks. Seven treatment-specific variants were found to predict opposite outcomes in surgery-only and surgery-plus-chemotherapy subgroups. Expression quantitative trait loci analysis indicated that six SNPs significantly correlated with their corresponding gene expression. T cells from high-risk subjects displayed reduced degranulation (p=0.02) and decreased cytotoxicity against cancer cells (p<0.01). Gene expression profile indicated increased IDO1 expression and decreased IL2, PRF and GZMB expression in high-risk subjects., Conclusions: Genetic variations in T cell cancer immune response pathways can impact outcomes and may be served as predictors for treatment efficacy in early-stage NSCLC patients. The correlation between immune genotypes and T cell antitumor immunity suggests a biological link between host immune genetics and NSCLC prognosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Recent studies highlight long non-coding RNAs (lncRNAs) as key regulators of cancer biology that contribute to carcinogenesis. The lncRNA HOXA transcript at the distal tip (HOTTIP) is involved in the development of several cancers. Previous studies demonstrated that HOTTIP could promote colorectal cancer (CRC) cell proliferation via silencing of p21 expression. However, the potential role of HOTTIP in CRC metastasis has not yet been discussed. Here, we found that HOTTIP level was significantly higher in CRC than in corresponding adjacent normal tissues, and patients with a larger tumor size, advanced pathological stage, or distant metastasis had higher HOTTIP expression. Moreover, silencing HOTTIP expression by siRNA or shRNA could inhibit CRC cell migration and invasion in vitro and in vivo, whereas HOTTIP overexpression promoted cell metastasis, as documented in the SW480 cell lines. Mechanistic analyses indicated that HOTTIP regulates CRC cell metastasis partly through the downregulation of tumor suppressor DKK1 expression. Collectively, our results suggest that tumor expression of lncRNA HOTTIP plays an important role in CRC metastasis. HOTTIP may serve as a candidate biomarker in this disease.

Genome-wide association studies (GWAS) have identified 13 susceptibility loci for renal cell carcinoma (RCC). Additional genetic loci of risk remain to be explored. Moreover, the role of germline genetic variants in predicting RCC recurrence and overall survival (OS) is less understood. In this study, we focused on 127 significantly mutated genes from The Cancer Genome Atlas (TCGA) Pan-Cancer Analysis across 12 major cancer sites to identify potential genetic variants predictive of RCC risk and clinical outcomes. In a three-phase design with a total of 2657 RCC cases and 5315 healthy controls, two single nucleotide polymorphisms (SNPs) that map to PIK3CG (rs6466135:A, ORmeta = 0.85, 95% CI = 0.77-0.94, Pmeta = 1.4 × 10-3) and ATM (rs611646:T, ORmeta = 1.17, 95% CI = 1.05-1.31, Pmeta = 3.5 × 10-3) were significantly associated with RCC risk. With respect to RCC recurrence and OS, two separate datasets with a total of 661 stages I-III RCC patients (discovery: 367; validation: 294) were analyzed. The most significant association was observed for rs10932384:C (ERBB4) with both outcomes (recurrence: HRmeta = 0.52, 95% CI = 0.39-0.68, Pmeta = 3.81 × 10-6; OS: HRmeta = 0.50, 95% CI = 0.37-0.67, Pmeta = 6.00 × 10-6). In addition, six SNPs were significantly associated with either RCC recurrence or OS but not both (Pmeta < 0.01). Rs10932384:C was significantly correlated with mutation frequency of ERBB4 in clear cell RCC (ccRCC) patients (P = 0.003, Fisher's exact test). Cis-eQTL was observed for several SNPs in blood/transformed fibroblasts but not in RCC tumor tissues. In summary, we identified promising genetic predictors of recurrence and OS among RCC patients with localized disease.

Objective: Mammalian target of rapamycin complex 1 (mTORC1) plays an important role in maintaining proper cellular functions in gastric cancer (GC). Previous studies demonstrated genetic variants within mTORC1 genes were associated with GC risk. However, no studies reported the associations between genetic variants within mTORC1 genes and GC prognosis. Herein, we firstly assessed the associations of genetic variants of mTORC1 genes with overall survival (OS) of GC in Chinese populations. Methods: We genotyped eight single nucleotide polymorphisms (SNPs) in mTORC1 genes (i.e., rs2536 T>C and rs1883965 G>A for mTOR , rs3160 T>C and rs26865 A>G for MLST8 , rs3751934 C>A, rs1062935 T>C, rs3751932 T>C and rs12602885 G>A for RPTOR ) by the TaqMan method in 197 Chinese GC patients who had surgical resection in Xinhua Hospital. We conducted Kaplan-Meier survival plots and Cox hazards regression analysis to explore the associations of these SNPs with OS. Results: The single-locus analysis indicated that RPTOR rs1062935 T>C was associated with an increased risk of poor GC prognosis (CC vs. TT/TC: adjusted Hazard ratio (HR) = 1.71, 95% confidence interval (CI) = 1.04-2.82). The combined analysis of all eight SNPs showed that patients with more than three risk genotypes significantly increased risk of death (adjusted HR = 2.44, 95% CI = 1.30-4.58), when compared to those with three or less risk genotypes. Conclusions: Our findings indicated that genetic variants within mTORC1 genes may predict GC prognosis in Chinese populations. The results need to be validated in future studies with larger sample sizes., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Objectives: The aim of this study was to evaluate the expression of RBM38 protein in gastric cancer patients and to explore its association with clinical pathological characteristics and prognosis., Materials and Methods: A total of 120 pairs of gastric cancer tissues and non-cancerous gastric mucosa from 120 patients who underwent gastrectomy for gastric cancer were included in the current study. RBM38 protein expression levels were detected in all tissue specimens by immunohistochemistry staining. The positive rate of RBM38 was compared between cancer tissue and normal tissue, and its association with the clinical pathological characteristics and prognosis was elucidated., Results: RBM38 protein was predominantly expressed in the cytoplasm of epithelial cells. The percentage of tissues with high RBM38 protein expression level was significantly lower (χ 2 =28.972, P<0.001) in gastric cancer tissues compared with adjacent non-cancerous gastric mucosal tissues. The expression level of RBM38 protein was associated with tumor size (P=0.028), depth of invasion (P<0.001), lymph node metastasis (P<0.001), TNM stage (P<0.001) and Lauren classification of the tumor (P=0.001), whereas it was not associated with gender (P=0.066) and age (P=0.6) of patients. Moreover, we noticed that the low expression level of RBM38 protein was also associated with poor prognosis in gastric cancer patients (log rank =5.325; P=0.021)., Conclusion: Overall, our findings indicated that RBM38 may play a vital role as a tumor suppressor, which may be a potential marker in the diagnosis and prognosis of gastric cancer., Competing Interests: None., (IJCEP Copyright © 2017.)

Background: Previous studies have shown that human epidermal growth factor receptor 2 (HER2) may play an important role in the invasion and metastasis of pancreatic cancer, but the relationship between HER2 amplification level and prognosis of pancreatic cancer patients is still controversial. Therefore, we performed a meta-analysis to determine the prognostic significance of HER2 amplification based on fluorescence in situ hybridization (FISH) in patients with pancreatic cancer., Methods: PubMed, EMBASE, and Web of Science (Jan 2001 to Jun 2015) were searched. Only articles that detect the HER2 amplification by FISH method were included. RevMan 5.3 and STATA version 12 were used to perform this meta-analysis. Pooled calculations were carried out on hazard ratio (HR) and 95% confidence interval (CI) to assess the risk of disease., Results: A total of six eligible studies were enrolled in meta-analysis. The univariate analysis results showed that HER2 amplification was not significantly associated with patients' overall survival (pooled HR, 1.87, 95% CI, 0.64-5.46, P=0.25), which are maintained in one study of multivariate analysis (HR 0.51, 95% CI, 0.12-2.14, P=0.358). HER2 amplification also had no correlation with clinicopathological factors such as age, gender, lymph node metastasis, and tumor stage., Conclusions: Our results showed that HER2 amplification based on FISH may not be a good prognostic factor for survival in patients with pancreatic cancer.

CD133 is one of the most commonly used markers of pancreatic cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity. Although the expression of CD133 has been reported to correlate with poor prognosis of PDAC in most literatures, some controversies still exist. In this study, we aimed to investigate the correlation between CD133 expression and prognosis and clinicopathological features in PDAC. A search in the Medline, EMBASE and Chinese CNKI (China National Knowledge Infrastructure) database (up to 1 March 2015) was performed using the following keywords pancreatic cancer, CD133, AC133, prominin-1 etc. Data from eligible studies were extracted and included into meta-analysis using a random effects model. Outcomes included overall survival and various clinicopathological features. We performed a final analysis of 723 patients from 11 evaluable studies for prognostic value and 687 patients from 12 evaluable studies for clinicopathological features. Our study shows that the pooled hazard ratio (HR) of overexpression CD133 for overall survival in PDAC was 0.58 (95% confidence interval (CI): 0.49-0.67) by univariate analysis and 0.73 (95% CI: 0.52-1.03) by multivariate analysis. With respect to clinicopathological features, CD133 overexpression by immunohistochemistry (IHC) method was closely correlated with clinical TNM stage (TNM stage III+IV, OR=0.32, 95% CI: 0.19-0.54), tumor differentiation (poor differentiation, OR=0.56, 95% CI: 0.37-0.83), and lymph node metastasis (N1, 3.15, 95% CI: 1.56-6.36) in patients with PDAC. Our meta-analysis results suggest that CD133 is an efficient prognostic factor in PDAC. Overexpression of CD133 was significantly associated with clinical TNM stage, tumor differentiation and lymph node metastasis.