Targeting translation regulators improves cancer therapy.

Deregulation of protein synthesis may be involved in multiple aspects of cancer, such as gene expression, signal transduction and drive specific cell biological responses, resulting in promoting cancer growth, invasion and metastasis. Study the molecular mechanisms about translational control may help us to find more effective anti-cancer drugs and develop novel therapeutic opportunities. Recently, the researchers had focused on targeting translational machinery to overcome cancer, and various small molecular inhibitors targeting translation factors or pathways have been tested in clinical trials and exhibited improving outcomes in several cancer types. There is no doubt that an insight into the class of translation regulation protein would provide new target for pharmacologic intervention and further provide opportunities to develop novel anti-tumor therapeutic interventions. In this review, we summarized the developments of translational control in cancer survival and progression et al, and highlighted the therapeutic approach targeted translation regulation to overcome the cancer.

Integrative analyses identify a DNA damage repair gene signature for prognosis prediction in lower grade gliomas.

Background: The DNA damage repair (DDR) pathways play important roles for regulating cancer progression and therapeutic response. IDH mutations, well-known prognosis biomarkers for glioma, lead to hypermethylation of tumor cells and affect genes' expression. Whether IDH mutations affect glioma prognosis through influencing the expression of DDR genes remains unclear. Methods: A total of 272 DDR genes were selected for differential expression and survival analysis. The identified genes were then utilized to construct the prognosis predicting model. Results: PARPBP, PLK3, POLL and WEE1 were found differential expressed between IDH mutations carriers and wild-type carriers, and were associated with survival of low grade glioma (LGG) patients. The predicting algorithm can predicts the prognosis of LGG patients. Conclusion: IDH mutations may affect LGG prognosis through regulation of DDR pathways.

Oral vitamin D supplementation has a lower bioavailability and reduces hypersecretion of parathyroid hormone and insulin resistance in obese Chinese males.

OBJECTIVE: To examine the vitamin D status, SNP of the vitamin D receptor gene (VDR) and the effects of vitamin D supplementation on parathyroid hormone and insulin secretion in adult males with obesity or normal weight in a subtropical Chinese city. DESIGN: An intervention trial. SETTING: Shenzhen City, Guangdong Province, China. SUBJECTS: From a cross-sectional survey conducted from June to July, eighty-two normal-weight and ninety-nine obese males (18-69 years) were screened to analyse their vitamin D status and for five SNP of VDR. From these individuals, in the same season of a different year, obese and normal-weight male volunteers (twenty-one per group) were included for an intervention trial with oral vitamin D supplementation at 1250 µg/week for 8 weeks. RESULTS: For the survey, there was no significant difference (P>0·05) in baseline circulating 25-hydroxyvitamin D concentrations or in the percentages of participants in different categories of vitamin D status between the two groups. The VDR SNP, rs3782905, was significantly associated with obesity (P=0·043), but none of the examined SNP were correlated with serum 25-hydroxyvitamin D when adjusted for age, BMI and study group. After vitamin D supplementation, serum 25-hydroxyvitamin D concentration, hypersecretions of parathyroid hormone and insulin, and insulin resistance in the obese were changed beneficially (P<0·05); however, the increase in serum 25-hydroxyvitamin D was less than that of the normal-weight men. CONCLUSIONS: For obese and normal-weight men of subtropical China, the summer baseline vitamin D status was similar. However, oral vitamin D supplementation revealed a decreased bioavailability of vitamin D in obese men and ameliorated their hypersecretion of parathyroid hormone and insulin resistance.

[Molecular characteristics of Neisseria gonorrhoeae isolates with decreased susceptibilities to ceftriaxone in Shenzhen from 2009 to 2011].

OBJECTIVE: To investigate the genotype and characteristics of Neisseria gonorrhoeae (N.gonorrhoeae) isolates with reduced susceptibility to ceftriaxone in Shenzhen from 2009 to 2011. METHODS: A total of 296 N.gonorrhoeae isolates were collected in Shenzhen from 2009 to 2011.ceftriaxone strains (minimum inhibitory concentration between 0.06 and 0.50 µg/ml) were determined by agar dilution method.Logistic regression was used to analyze the associated factors of ceftriaxone N.gonorrhoeae infection.Neighbor-joining (NJ) phylogenetic tree analysis and N.gonorrhoeae multi antigen sequence typing (NG-MAST) were performed on all ceftriaxone isolates and susceptible control isolates randomly selected in accordance with the principle of 1: 1 sampling. RESULTS: No isolates displayed resistance to ceftriaxone, whereas 53(17.9%) showed reduced susceptibility to ceftriaxone among 296 isolates.Only antibiotic use in recent two months was associated with ceftriaxone isolates infection (OR = 3.080, 95%CI: 1.376-6.894) . Among the ceftriaxone isolates, 48 different ST were identified including 5 STs (ST1768, ST3927, ST641, ST7076 and ST7078) containing 2 isolates and 43 single STs. There were 26 STs previously reported from HongKong in China.Low sensitive strains clustering was not observed by NJ phylogenetic tree. CONCLUSION: The proportion of ceftriaxone strains among the 296 N.gonorrhoeae isolates collected from 2009 to 2011 in Shenzhen is high. The STs of ceftriaxone strains may have unique epidemic features in Shenzhen.

Association of variations in the Fanconi anemia complementation group and prognosis in Non-small cell lung cancer patients with Platinum-based chemotherapy.

PURPOSE: To explore the associations between FANC (FANCA, FANCC, FANCE, FANCF, and FANCJ) single nucleotide polymorphisms (SNPs) and prognosis of non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy. METHODS: According to the inclusion criteria, we selected 395 DNA samples from NSCLC patients for genotyping and combined with clinical data for Cox regression analysis and stratification analyses to assess relationships between overall survival (OS) and progression free survival (PFS) with SNPs genotypes. RESULTS: The results revealed that patients with FANCE rs6907678 TT genotype have a longer OS than TC and CC genotype (Additive model: P = 0.004, HR = 1.696, 95% CI = 1.186-2.425). In stratification analyses, Longer PFS is found in female, age ≤ 55 years old and non-smoking patients with FANCE rs6907678 TT genotype, and patients with TT genotypes were significantly had longer OS in male, age ＞55 years old, non-smoking, squamous cell carcinoma and stage IV stratification. CONCLUSION: Our data demonstrates that patients with FANCE rs6907678 TT genotype are contributed to better prognosis. FANCE rs6907678 may be used as a clinical biomarker for predicting the prognosis of NSCLC patients with platinum-based chemotherapy.

PARP-1 overexpression does not protect HaCaT cells from DNA damage induced by SiO2 nanoparticles.

Nano-SiO2 is increasingly used in diagnostic and biomedical research because of its ease of production and relatively low cost and which is generally regarded as safe and has been approved for use as a food or animal feed ingredient. Although recent literature reveals that nano-SiO2 may present toxicity and DNA damage, however, the underlying mechanism remains poorly understood. Since in previous studies, we found that nano-SiO2 treatment down-regulated the expression of the poly(ADP-ribose) polymerases-1 (PARP-1), a pivotal DNA repair gene, in human HaCaT cells and PAPR-1 knockdown can aggravate DNA damage induced by nano-SiO2. Therefore, we speculate whether PARP-1 overexpression can protect DNA from damage induced by nano-SiO2. However, our data demonstrated that overexpression of PARP-1 in HaCaT cells slightly enhanced the cellular proliferation of undamaged cells, when compared with both empty vector control cells and parental cells, but had drastic consequences for cells treated with nano-SiO2. The PARP-1 overtransfected cells were sensitized to the cytotoxic effects and DNA damage of nano-SiO2 compared with control parental cells. Meanwhile, flow cytometric analysis of nano-SiO2 stimulated poly(ADP-ribose) synthesis revealed consistently larger fractions of cells positive for this polymer in the PARP-1 overexpression cells than in control clones. Combining our previous research on PARP-1 knockdown HaCaT cells, we hypothesize that an optimal level of cellular poly(ADP-ribose) accumulation exists for the cellular recovery from DNA damage.

Association between CASC16 rs4784227 polymorphism and breast cancer susceptibility: A meta-analysis.

OBJECTIVE: To explore whether rs4784227 polymorphism of CASC16 is correlated with risk of breast cancer. METHODS: Relevant studies up to December 24, 2020 were searched in PubMed, Embase, Web of Science, CNKI, VIP, and WANFANG databases. Data were analyzed by using Stata 12.0. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and country-based subgroup analyses were conducted. Sensitivity analysis was conducted to assess the stability of the results. Publication bias was assessed by using the Egger regression asymmetry test and visualization of funnel plots. RESULTS: Seven case-control studies enrolling 4055 breast cancer cases and 4229 controls were included. rs4784227 was found significantly associated with increased risk of breast cancer in a dominant (OR = 1.301, 95% CI = 1.190-1.423, P < .001), a recessive (OR = 1.431, 95% CI = 1.216-1.685, P < .001), and an allele model (OR = 1.257, 95% CI = 1.172-1.348, P < .001), while an over-dominant model showed that rs4784227 was correlated with decreased breast cancer risk (OR = 0.852, 95% CI = 0.778-0.933, P = .001). CONCLUSION: The rs4784227 polymorphism of CASC16 gene is correlated with breast cancer susceptibility.

Pharmacogenomics of 5-fluorouracil in colorectal cancer: review and update.

BACKGROUND: Colorectal cancer (CRC) is a disease with high morbidity and mortality rates. 5-fluorouracil (5-FU) is the first-line recommended drug for chemotherapy in patients with CRC, and it has a good effect on a variety of other solid tumors as well. Unfortunately, however, due to the emergence of drug resistance the effectiveness of treatment may be greatly reduced. In the past decade, major progress has been made in the field of 5-FU drug resistance in terms of molecular mechanisms, pre-clinical (animal) models and clinical trials. CONCLUSIONS: In this article we systematically review and update current knowledge on 5-FU pharmacogenomics related to drug uptake and activation, the expression and activity of target enzymes (DPD, TS and MTHFR) and key signaling pathways in CRC. Furthermore, a summary of drug combination strategies aimed at targeting specific genes and/or pathways to reverse 5-FU resistance is provided. Based on this, we suggest that causal relationships between genes, pathways and drug sensitivity should be systematically considered from a multidimensional perspective. In the design of research methods, emerging technologies such as CRISPR-Cas, TALENS and patient-derived xenograft models should be applied as far as possible to improve the accuracy of clinically relevant results.