Journal of Cancer Prevention最新文献

The tumor microenvironment (TME) is a decisive determinant of therapeutic response and the emergence of drug resistance in lung cancer. Among its stromal constituents, mesenchymal stem cells (MSCs) are pivotal regulators of disease progression because they secrete diverse paracrine mediators. Accumulating evidence indicates that MSC-derived cytokines, growth factors, and extracellular vesicles (EVs) drive epithelial-mesenchymal transition (EMT)-a phenotypic shift that augments cellular motility, invasiveness, and stem-like traits. EMT contributes directly to resistance against epidermal growth factor receptor tyrosine kinase inhibitors and platinum-based chemotherapy. Key MSC-secreted factors, such as TGF-β1, interleukin-6, and C-C motif chemokine ligand 5, activate signal transducer and activator of transcription 3, phosphoinositide 3-kinase/AKT, and Wnt/β-catenin cascades, thereby reinforcing drug-resistant phenotypes. MSC-induced EMT also remodels immune surveillance and supports the persistence of residual tumor clones. Elucidating the molecular reciprocity between MSCs and lung cancer cells within the TME is indispensable for rational therapy design. This review synthesizes current mechanistic insights into MSC-mediated EMT-driven resistance and discusses translational strategies including targeted inhibition of paracrine signaling and EV engineering that may restore drug sensitivity in lung cancer.

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with genetic, epigenetic, and immune-dependent mechanisms contributing to disease pathogenesis. Preventive strategies are especially important for individuals with hereditary syndromes such as familial adenomatous polyposis (FAP), in which Adenomatous Polyposis Coli (APC) mutations drive early tumor formation. The polyposis in rat colon (Pirc) model, harboring an Apc mutation, faithfully recapitulates the development of adenomatous polyps, a precursor stage of CRC, in both the colon and duodenum. Here, we report the generation and characterization of primary cell cultures derived from 30 colonic and duodenal adenomas (benign tumors) from Pirc rats. These Pirc colon adenoma and duodenal adenoma cultures demonstrated consistent morphology, epithelial marker expression (E-cadherin and pan-cytokeratin), and robust 3D spheroid formation. Growth kinetics revealed a doubling time of 50 ± 4 hours. Notably, histone deacetylase and bromodomain inhibitors reduced cell viability and colony formation significantly, highlighting the synergistic potential in targeting deregulated epigenetic signatures as early-stage prevention strategies in FAP. These primary cultures, maintained between passages 5 and 10 to preserve phenotypic integrity, offer a valuable ex vivo model for early-stage CRC research and the screening of preventive agents. By bridging genetic susceptibility and translational prevention, this platform provides a novel and reproducible tool for advancing cancer interception.

Keratinocyte carcinomas (KC) are the most frequent cancers diagnosed in Australia and impart the largest economic cost of all cancers. Predisposed individuals tend to develop multiple KC over their lifetime. Data from the ASPirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial with post-trial observational follow up (ASPREE-eXTension) were analysed, to compare the KC incidence among older Australians randomized to daily 100 mg aspirin or placebo, and to determine whether aspirin influenced multiple primary KC development. Participants were linked to the Medicare Benefits Schedule for KC ascertainment; medical history was collected at ASPREE enrolment. A Cox proportional hazards model was used to estimate hazard ratios (HR) for KC incidence, and was adjusted for age, sex and race. The Anderson and Gill recurrent event model compared the incidence of multiple KC between aspirin and placebo groups. Thirteen thousand eight hundred thirty-eight participants (6,850 aspirin treated, 6,988 placebo) were analysed over median 6.8 years (trial period 4.7 years); 36.1% developed a KC and 20.7% developed multiple primary KCs. Randomization to aspirin was not significantly associated with KC incidence, (adjHR = 0.97, 95% CI [0.92 to 1.03], P = 0.31). However, it did decrease the rate of multiple KC development (adjHR = 0.93, 95% CI [0.88 to 0.99], P = 0.02). This post-hoc analysis of a large trial with post-trial observational follow-up showed that aspirin did not influence the incidence, but decreased the rate of multiple KC.

Cancer survivors may exhibit biological and metabolic changes linked to both cancer and its treatment. This systematic review aimed to compare metabolic and biological aging-related biomarkers between cancer survivors and healthy individuals. The primary electronic databases utilized to search papers from 2019 to 2024 were PubMed, Scopus, and Web of Science. Boolean operators were combined with specific keywords and MESH terms in searching the articles. After excluding protocol papers, studies with incorrect designs or populations, and animal studies, 27 articles were selected for data extraction, synthesis, and quality evaluation. The articles were checked for quality by using the National Institutes of Health (NIH) checklist for observational cohort and cross-sectional studies. Cancer survivors had significant differences in aging-related metabolic and biological biomarkers compared to a healthy population. These include aberrant DNA methylation (hypermethylation, hypomethylation, and epigenetic modification), abnormal expression levels of lipid profiles (high-density lipoprotein, low-density lipoprotein level, malondialdehyde, and apolipoprotein C-1), inflammatory markers (interleukins, C-reactive protein, and TNF-α), immune-senescence (Cellular Communication Network Factor 3 protein), energy regulation (leptin, adiponectin, and mitochondria function profiles), and poor oral and bone health. These findings reflect the accelerated biological age and increased vulnerability to age-related diseases among cancer survivors, as compared to healthy populations. However, considering the cross-sectional design limitations, causal relationships between cancer diagnosis and alterations in biological aging cannot be confirmed. To establish whether cancer itself contributes to accelerated aging, future longitudinal studies are needed that assess metabolic and biological biomarkers in individuals from the time of diagnosis onward.

Hepatocellular carcinoma (HCC) is a highly malignant liver cancer that metastasizes to various organs. Esculetin, a natural dihydroxy coumarin derivative, has been shown to have a variety of pharmacological properties, including immune-enhancing, antioxidant, and anti-inflammatory effects. Esculetin is also known to have potent anticancer activity; however, studies on its ability to inhibit cancer cell metastasis are relatively rare. In this study, we investigated how esculetin inhibits the migration and invasion of human hepatocellular carcinoma cell lines Hep3B and HepG2, and elucidated the underlying mechanisms. Our results showed that esculetin markedly suppressed the migration and invasion of HCC cells, and this was associated with a decrease in the expression and activity of matrix metalloproteinase (MMP)-9 and MMP-2, and increased expression levels of tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2. In addition, esculetin enhanced the tightening of tight junctions by suppressing the expression of claudin family proteins.

Keratinocyte cancer burden is escalating, particularly in older Australian adults, where the incidence was > 6,000/100,000 in persons aged 80 to 84 per year, compared with 26/100,000 in persons aged 20 to 24 per year, in Queensland between 2011 to 2014. Keratinocyte cancers are estimated to account for 25% of all cancer-related hospitalisations and > $1 billion in treatment costs per year in Australlia. This undoubtedly leads to a large strain on the medical system, as well as amplifying patient morbidity and mortality. Those who are immunosuppressed, or with haematological malignancy or a solid organ transplant, are typically at highest risk of developing a keratinocyte cancer; however, older adults, and especially UV exposed Caucasian populations are increasingly requiring treatment for several keratinocyte cancers every year. This has resulted in an acute, urgent need for efficacious, tolerable, safe chemoprevention agents that could decrease keratinocyte cancer burden. Aspirin has been investigated as a chemopreventive agent for many years in other cancers. In this narrative review, the role for aspirin in the chemoprevention of keratinocyte cancers is discussed.

[This corrects the article on p. 134 in vol. 23, PMID: 30370258.].

To date, no studies have examined the effect of high-density lipoprotein cholesterol (HDL-C) on the development of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). We investigated, for the first time, the relationship between HDL-C and the risk of MALT lymphoma. In this nationwide population-based cohort study, 4.25 million cancer-free individuals that underwent a National General Health Examination and cancer screening in 2010 were enrolled and followed until the end of 2017. Subjects were classified into 5 groups based on HDL-C levels (< 30, 30-39, 40-49, 50-59, or ≥ 60 mg/dL). MALT lymphoma was diagnosed in 1,119 of the 4.25 million study subjects during the follow-up period. Subjects with the lowest HDL-C level (< 30 mg/dL) had a higher risk of MALT lymphoma (adjusted hazard ratio [aHR] 1.79, 95% CI 1.08-2.96) than those with a HDL-C level of 40 to 49 mg/dL, whereas those with the highest HDL-C level (≥ 60 mg/dL) had a lower risk of MALT lymphoma (aHR 0.84, 95% CI 0.71-0.99). Sensitivity analyses, excluding individuals who were diagnosed with MALT lymphoma within 2-year of follow-up, also revealed similar association. In subgroup analysis, the hazardous effect of low HDL-C on MALT lymphoma development was significant in females (aHR 2.31, 95% CI 1.13-4.72) but not in males. An unfavorable effect of low HDL-C on MALT lymphoma was significant in never smokers (aHR 2.20, 95% CI 1.19-4.05) but not in smokers. In conclusion, a low HDL-C level was found to be associated with an increased risk of MALT lymphoma particularly in females or never smokers.

The objective of this study was to consolidate the mounting evidence related to the association between fruit and vegetable intake and lung cancer risk by conducting a systematic review of prospective studies and a dose-response meta-analysis. A systematic search was conducted on major online databases (PubMed, Scopus, and Web of Science) from inception up to January 2024. The exposures included daily intake of total fruits and vegetables (FVs), vegetables, fruits, and their subclasses (including cruciferous and green leafy vegetables, and citrus fruits). The main outcome was lung cancer and its subclasses (incidence and mortality). Out of 31,819 records initially retrieved, 41 eligible studies were included. Significant inverse associations were observed between lung cancer and daily consumption of total FVs (risk ratios [RR]: 0.81, 95% CI: 0.74-0.90), vegetables (RR: 0.87, 95% CI: 0.83-0.91), fruits (RR: 0.78, 95% CI: 0.72-0.85), cruciferous vegetables (RR: 0.82, 95% CI: 0.75-0.91), green leafy vegetables (RR: 0.85, 95% CI: 0.76-0.94), and citrus fruits (RR: 0.80, 95% CI: 0.73-0.88). Non-linear dose-response associations were observed regarding lung cancer and all of the exposures, except for cruciferous vegetables. The consumption of FVs may decrease the risk of lung cancer incidence and mortality. The type of lung cancer, biological sex of individuals, and smoking status can alter this association.

Cirrhosis has a very high morbidity and mortality and partially progressed into hepatocellular carcinoma (HCC). Sevelamer is an oral phosphate binder to treat hyperphosphatemia. Here, we investigated the contribution of sevelamer to the remission of cirrhosis, and further the prevention of HCC. Diethylnitrosamine (DEN)-treated rats, developing the sequential stage of cirrhosis to HCC, were used to identify the therapeutic and preventive effects via transient elastography, hematological biochemistry, and pathological examination. Ultrasound image and transient elastography are indicative of the occurrence of cirrhosis characterized by the pseudolobular formation and higher stiffness after DEN exposure, and few nodules and lower stiffness values were observed in the control and sevelamer treated group. Hematological biochemistry showed that indicators of liver fibrosis (serum hyaluronic acid and type III precollagen) and serum tumor biomarkers (VEGF-α, α-L-fucosidase) were also simultaneously reversed. Pathological examination showed that hepatic steatosis, inflammation, and fibrotic deposits were remarkably alleviated after sevelamer administration. The pharmacology of sevelamer might be attributable to rebalance of oxidative stress as assessed by determination of the total reactive oxygen specie, malondialdehyde and antioxidant enzymes, to modulation of inflammation as evidenced by decreased interleukin (IL)-1β, IL-4, IL-6 and TNFα levels, and to inhibition of angiogenesis as measured by microvessel density. Our findings confirm that sevelamer reverses cirrhosis and prevents its deterioration to in the DEN-induced rat HCC model.