Research Progress of Carrier-Free Antitumor Nanoparticles Based on Phytochemicals

Cancer is a major worldwide public health issue, responsible for millions of deaths every year. Cancer cases and deaths are expected to increase rapidly with population growth, age, and lifestyle behaviors that increase cancer risk. Long-term chemotherapy results in acquired drug resistance. Traditional treatment methods have limitations and cannot effectively treat distal metastatic cancers. Application of nanocarriers in multi-chemotherapy must be promoted. With research progress, the shortcomings of traditional nanocarriers have gradually become evident. Carrier-free nanodrugs with desirable bioactivity have attracted considerable attention. In this review, we provide an overview of recent reports on several carrier-free nanodrug delivery systems based on phytochemicals. This review focuses on the advantages of carrier-free nanodrugs, and provides new insights for establishment of ideal cancer treatment nanosystems.

739 Pancreatic Cancer and Bariatric Surgery: Narrative Review

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest types of cancer with an estimated incidence of 8 per 100,000 person-years and mortality of 7 per 100,000 person-years worldwide. Method A narrative review of the literature was conducted. PubMed, Web of Science and Cochrane database were searched for all published papers in Pancreatic cancer post Bariatric surgery from 1990 to November 2020. Results Epidemiological evidence in the literature has shown that obesity as a risk factor for the development of PDAC is a dose dependent risk. The review found that the risk of developing pancreatic cancer in obese or overweight individuals is 1.5 times higher than individuals with a normal BMI. At the same time, evidence from literature demonstrated that weight reduction by dietary restriction, physical activities, pharmacotherapy or weight reduction surgery reduces risk of PDAC.A total of 24 cases of pancreatic cancer were identified in the literature reported post Bariatric Surgery. The average age at diagnosis was 57.2 years and onset from surgery to diagnosis ranged from 2 months to 25 years. Of the identified cases, 23 cases were post Roux-en-Y Gastric Bypass and one case post Duodenal Switch. The review found that PDAC was the commonest reported pancreatic cancer post bariatric surgery accounting for 85.3%, followed by Neuroendocrine Tumours (NET) 16.7%. Given the variation in onset of diagnosis, bariatric surgery did not increase cancer risk but rather accelerated the diagnosis of pancreatic cancer. Conclusions Along with weight reduction and improving comorbidities, Bariatric surgery reduces risk of obesity-related carcinogenesis.

Association of Polymorphisms in Vitamin D-Metabolizing Enzymes DHCR7 and CYP2R1 with Cancer Susceptibility: A Systematic Review and Meta-Analysis

The deficiency of vitamin D has been reported to be relevant to cancer risk. DHCR7 and CYP2R1 are crucial components of vitamin D-metabolizing enzymes. Thus, accumulating researchers are concerned with the correlation between polymorphisms of DHCR7 and CYP2R1 genes and cancer susceptibility. Nevertheless, the conclusions of literatures are inconsistent. We conducted an integrated review for the correlation of DHCR7 and CYP2R1 SNPs with cancer susceptibility. In the meanwhile, a meta-analysis was performed using accessible data to clarify the association between DHCR7 and CYP2R1 SNPs and overall cancer risk. Literatures which meet the rigid inclusion and exclusion criteria were involved. The association of each SNP with cancer risk was calculated by odds ratios (ORs). 12 case-control designed studies covering 23780 cases and 27307 controls were ultimately evolved in the present meta-analysis of five SNPs (DHCR7 rs12785878 and rs1790349 SNP; CYP2R1 rs10741657, rs12794714, and rs2060793 SNP). We found that DHCR7 rs12785878 SNP was significantly related to cancer risk in the whole population, Caucasian subgroup, and hospital-based (HB) subgroup. DHCR7 rs1790349 SNP was analyzed to increase cancer risk in Caucasians. Moreover, CYP2R1 rs12794714-A allele had correlation with a lower risk of colorectal cancer. Our findings indicated that rs12785878, rs1790349, and rs12794714 SNPs might potentially be biomarkers for cancer susceptibility.

Ethylene Oxide Exposure in U.S. Populations Residing Near Sterilization and Other Industrial Facilities: Context Based on Endogenous and Total Equivalent Concentration Exposures

Given ubiquitous human exposure to ethylene oxide (EO), regardless of occupation or geography, the current risk-specific concentrations (RSCs: 0.0001–0.01 ppb) from the U.S. Environmental Protection Agency (EPA) cancer risk assessment for EO are not useful metrics for managing EO exposures to the general U.S. population. The magnitude of the RSCs for EO are so low, relative to typical endogenous equivalent metabolic concentrations (1.1–5.5 ppb) that contribute ~93% of total exposure, that the RSCs provide little utility in identifying excess environmental exposures that might increase cancer risk. EO monitoring data collected in the vicinity of eight EO-emitting facilities and corresponding background locations were used to characterize potential excess exogenous concentrations. Both 50th and 90th percentile exogenous exposure concentrations were combined with the 50th percentile endogenous exposure concentration for the nonsmoking population, and then compared to percentiles of total equivalent concentration for this population. No potential total exposure concentration for these local populations exceeded the normal total equivalent concentration 95th percentile, indicating that excess facility-related exposures are unlikely to require additional management to protect public health.

Functional analysis of genetic variants in the high-risk breast cancer susceptibility gene PALB2

Heterozygous carriers of germ-line loss-of-function variants in the DNA repair gene PALB2 are at a highly increased lifetime risk for developing breast cancer. While truncating variants in PALB2 are known to increase cancer risk, the interpretation of missense variants of uncertain significance (VUS) is in its infancy. Here we describe the development of a relatively fast and easy cDNA-based system for the semi high-throughput functional analysis of 48 VUS in human PALB2. By assessing the ability of PALB2 VUS to rescue the DNA repair and checkpoint defects in Palb2 knockout mouse embryonic stem (mES) cells, we identify various VUS in PALB2 that impair its function. Three VUS in the coiled-coil domain of PALB2 abrogate the interaction with BRCA1, whereas several VUS in the WD40 domain dramatically reduce protein stability. Thus, our functional assays identify damaging VUS in PALB2 that may increase cancer risk.

Alkoholkonsum und Krebsrisiko

Alcohol use is one of the most important and potentially modifiable risk factors for cancer in Germany. The more and the longer a person drinks, the higher the risk of cancer. Even modest use of alcohol may increase cancer risk. Statistically, every German drinks more than 100 gram of alcohol per week; this amount is currently considered to be the limit of low-risk use. Alcohol is causally associated with oropharyngeal and larynx cancer, esophageal squamous cell cancer, hepatocellular carcinoma, breast cancer, and colorectal cancer. People with long-term risky alcohol use should be encouraged to join programs of cancer screening. Alcohol cessation appears to be effective in reducing the alcohol-induced, increased cancer risk.

Consumption of Sugars, Sugary Foods, and Sugary Beverages in Relation to Cancer Risk: A Systematic Review of Longitudinal Studies

High sugar intake may increase cancer risk by promoting insulin–glucose dysregulation, oxidative stress, inflammation, and body adiposity, but epidemiologic evidence is unclear. Associations between dietary sugars and lifestyle-related cancer risk from longitudinal studies were evaluated. We systematically searched PubMed, Embase, and CINAHL and identified 37 prospective cohort studies (1990–2017) reporting multivariable adjusted risk estimates for dietary sugars in relation to cancer. Of 15 and 14 studies on total sugar and sucrose respectively, 11 reported a null association in relation to cancer. Of 14 studies on fructose, 8 reported null associations, and 2 reported protective and 4 reported detrimental associations. In two of five studies on added sugars, a 60–95% increased cancer risk was observed with higher intakes. In 8 of 15 studies on sugary foods and beverages, a 23–200% higher cancer risk was observed with higher sugary beverage consumption. In conclusion, most studies were indicative of a null association, but suggestive detrimental associations were reported for added sugars and sugary beverages.