Journal of Cancer Prevention最新文献

Silent mating type information regulator 2 homolog 1 (SIRT1), an NAD⁺-dependent histone/protein deacetylase, has multifarious physiological roles in development, metabolic regulation, and stress response. Thus, its abnormal expression or malfunction is implicated in pathogenesis of various diseases. SIRT1 undergoes post-translational modifications, including phosphorylation, oxidation/reduction, carbonylation, nitrosylation, glycosylation, ubiquitination/deubiquitination, SUMOylation etc. which can modulate its catalytic activity, stability, subcellular localization, and also binding affinity for substrate proteins. This short review highlights the regulation of SIRT1 post-translational modifications and their pathophysiologic implications.

Vitamin D is considered to be the main mediator of the beneficial effects of sun exposure. In humans, highest expression of Vitamin D receptors is found in the intestinal tract. In addition, 1α,25-dihydroxyvitamin D3 (or calcitriol), the most active Vitamin D metabolite, plays important homeostatic roles in the intestine, particularly calcium absorption. Vitamin D deficiency is defined as a serum 25-hydroxyvitamin D [25(OH)D] level of < 20 ng/mL. Previous studies show that higher circulating 25(OH)D levels are associated with reduced risk of colorectal cancer (CRC) and improved survival. Most research to date has been conducted in animals, specifically mice. Although human studies have a limited number of participants, one study recruiting a large cohort of patients with advanced or metastatic CRC revealed that higher plasma 25(OH)D levels are associated with improved overall and progression-free survival. However, the effects of Vitamin D supplementation on incidence and mortality of CRC remain inconclusive. Although Vitamin D may help to prevent cancer, there is a paucity of research demonstrating conclusively that Vitamin D alters prognosis after chemotherapy. Here, we review the mechanisms by which Vitamin D affects CRC, as well as the results of clinical, epidemiological, and human intervention studies. We also discuss current perspectives and future directions regarding Vitamin D and CRC.

Emergence of radioresistance in prostate cancer (PCa) cells is a major obstacle in cancer therapy and contributes to the relapse of the disease. EGF receptor (EGFR) signaling plays an important role in the development of radioresistance. Herein, we have assessed the modulatory effects of silibinin on radiation-induced resistance via DNA repair pathways in EGFR-knockdown DU145 cells. shRNA-based silencing of EGFR was done in radioresistant human PCa DU145 cells and effects of ionizing radiation (IR) and silibinin were assessed using clonogenic and trypan blue assays. Furthermore, radiosensitizing effects of silibinin on PCa in context with EGFR were analyzed using flow cytometry, comet assay, and immunoblotting. Silibinin decreased the colony formation ability with an increased death of DU145 cells exposed to IR (5 Gray), with a concomitant decrease in Rad51 protein expression. Silibinin (25 μM) augmented the IR-induced cytotoxic effect in EGFR-knockdown PCa cells, along with induction of G2/M phase cell cycle arrest. Further, we studied homologous recombination (HR) and non-homologous end joining (NHEJ) pathways in silibinin-induced DNA double-strand breaks in EGFR-knockdown DU145 cells. Silibinin down-regulated the expression of Rad51 and DNA-dependent protein kinase proteins without any considerable effect on Ku70 and Ku80 in IR-exposed EGFR-knockdown PCa cells. The pro-survival signaling proteins, phospho-extracellular signal-regulated kinases (ERK)1/2, phospho-Akt and phospho-STAT3 were decreased by silibinin in EGFR-deficient PCa cells. These findings suggest a novel mechanism of silibinin-induced radiosensitization of PCa cells by targeting DNA repair pathways, HR and NHEJ, and suppressing the pro-survival signaling pathways, ERK1/2, Akt and STAT3, in EGFR-knockdown PCa cells.

Jaboticaba is a Brazilian berry, which is rich in fibers and bioactive compounds and shows high antioxidant and antiproliferative activities. Prostate cancer (PCa) is the second most common type of cancer among men and its progression is influenced by androgens and inflammation. Previous studies reported the ability of the jaboticaba to modulate pathways involved in prostate diseases. The main objective of this study was to provide significant data about molecular targets of the jaboticaba peel extract (JPE) and its mechanisms of action in PCa cell lines with different androgenic status (LNCaP and PC-3). The results showed that JPE was able to decrease cell viability in both cell lines. LNCaP showed more sensitivity to JPE exposure, indicating the efficacy of the JPE treatment in terms of androgen responsiveness. JPE showed a distinct hormone dependent effect on the NF-κB signaling, with reduced NF-κB levels for LNCaP and increased NF-κB levels in PC-3 cells. Mechanisms related to cell death by apoptosis were stimulated after the JPE treatment, modulating B-cell lymphoma 2 and BAX for LNCaP and PC-3. Particularly for PC-3, the JPE treatment resulted in cytokine-cytokine receptor interaction activation mostly by up regulating pro-inflammatory, pro-angiogenic, immunostimulatory and immunosuppressive genes. Also, a set of genes related to angiogenesis and metastasis were down-regulated by JPE. In conclusion, JPE exerted an antitumor effect on PCa for both cell lines which can be enhanced if androgenic reliance is considered.

Colorectal cancer (CRC) is a disease with high prevalence and mortality. Estimated preventability for CRC is approximately 50%, indicating that altering modifiable factors, including diet and body weight, can reduce CRC risk. There is strong evidence that dietary factors including whole grains, high-fiber, red and processed meat, and alcohol can affect the risk of CRC. An alternative strategy for preventing CRC is use of a chemopreventive supplement that provides higher individual exposure to nutrients than what can be obtained from the diet. These include calcium, vitamin D, folate, n-3 polyunsaturated fatty acids, and phytochemicals. Several intervention trials have shown that these dietary chemopreventives have positive protective effects on development and progression CRC. Research on chemoprevention with phytochemicals that possess anti-inflammatory and/or, anti-oxidative properties is still in the preclinical phase. Intentional weight loss by bariatric surgery has not been effective in decreasing long-term CRC risk. Physicians should perform dietary education for patients who are at high risk of cancer for changing their dietary habits and behaviour. An increased understanding of the role of individual nutrients linked to the intestinal micro-environment and stages of carcinogenesis would facilitate the development of the best nutritional formulations for preventing CRC.

Most research on cancer patient survival uses registry-based (e.g., SEER) incidence and survival data that have limited socioeconomic status and health-risk information. In this study, we used the 1997-2015 National Health Interview Survey-National Death Index prospectively-linked pooled cohort database (n = 40,291 cancer patients) to examine disparities in patient survival by a broad range of social determinants, including race/ethnicity, nativity, educational attainment, income/poverty level, occupation, housing tenure, physical and mental health status, smoking, physical activity, body mass index, and alcohol consumption. We used Cox proportional hazards models to estimate mortality hazard ratios and cause-specific 1-year, 5-year, and 10-year survival rates for all-cancer and lung cancer. During 1997-2015, the 10-year age-adjusted (all-cause) survival rate for cancer patients with professional and managerial occupations was 89.66%, significantly higher than the survival rate of 83.17% for laborers or 83.66% for the unemployed. Cancer patients with renting house had significantly lower age-adjusted survival rates than those owning house (82.65% vs. 85.80%). The 10-year age-adjusted survival rates were significantly greater among cancer patients with regular physical activity than those without regular physical activity (90.18% vs. 83.24%). Age-adjusted survival rates were significantly reduced for cancer patients with lower income and education, poor health, and serious psychological distress, and among current and former smokers. The gap in survival narrowed with additional sociodemographic, health, or behavioral adjustment. Similarly large differentials were found in lung cancer survival. Marked disparities in all-cancer and lung cancer survival were found by a wide range of sociodemographic and health characteristics.

Osteosarcoma is the most frequent primary malignant bone tumor with higher incidences in children and adolescents. Despite clinical evolutions, patients with osteosacoma have had a poor prognosis. There has been increasing evidence that cancer is a stem cell disease. This study sought to isolate and characterize cancer stem cells from human osteosarcoma with relevant literature reviews. Here we show that the emerging evidence suggests osteosarcoma should be regarded as a differentiation disease such as stem cell disease. Two human osteosarcoma cell lines were cultured in non-adherent culture conditions as sarcospheres. Sarcospheres were observed using histomorphology and alkaline phosphatase (ALP) staining. Expression of the embryonic stem cell marker was analyzed with use of reverse transcriptase-PCR. Sarcospheres could be reproduced consistently throughout multiple passages and produced adherent osteosarcoma cell cultures. Expression of stem cell-associated genes such as those encoding Nanog, octamer-binding transcription factor 3/4, sex determining region Y box 2 , c-Myc and ALP indicated pluripotent stem-like cells. These results support the extension of the cancer stem cell theory to include osteosarcoma. Understanding the cancer stem cell derived from human osteosarcoma could lead to the evolution of diagnosis and treatment for osteosarcoma patients.

The incidence of colorectal cancer has considerably increased worldwide, particularly among adults aged 50 and older. Despite numerous nutrition initiatives, colorectal cancer (CRC) remains a public health burden that affects younger adults in the United States. Understanding the potential factors contributing to non-adherence to nutrition recommendations can be helpful to develop effective nutrition initiatives to prevent CRC. This study aimed to determine differences in nutrition knowledge, attitudes, and beliefs (KAB); examine their associations on diet characteristics and weight status; and identify factors influencing eating patterns among ethnically diverse populations at risk for CRC and living in urban areas. The study used a quantitative descriptive and correlational research design in which data were collected through an online cross-sectional survey. A total of 377 participants responded to the survey. The study revealed a few significant differences in KAB levels between males and females. KAB levels were not associated with weight status but with meat recommendations among overweight or obese males. Ultimately, the study identified perceived barriers and facilitators as factors influencing participants' diets. Differences in KAB among males and females were inconsistent with the diet characteristics and weight status variables. This study suggests acknowledging these differences and inconsistencies when designing nutrition initiatives focusing on colorectal cancer prevention.

Myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are bone marrow disorders characterized by cytopenias and progression to acute myeloid leukemia. Hypomethylating agents (HMAs) are Food and Drug Administration-approved therapies for MDS and MDS/MPN patients. HMAs have improved patients' survival and quality of life when compared with other therapies. Although HMAs are effective in MDS and MDS/MPN patients, they are associated with significant toxicities that place a large burden on patients. Our goal is to develop a safer and more effective HMA from natural products. We previously reported that black raspberries (BRBs) have hypomethylating effects in the colon, blood, spleen, and bone marrow of mice. In addition, BRBs exert hypomethylating effects in patients with colorectal cancer and familial adenomatous polyposis. In the current study, we conducted a pilot clinical trial to evaluate the hypomethylating effects of BRBs in patients with low-risk MDS or MDS/MPN. Peripheral blood mononuclear cells (PBMCs) were isolated before and after three months of BRB intervention. CD45⁺ cells were isolated from PBMCs for methylation analysis using a reduced-representation bisulfite sequencing assay. Each patient served as their own matched control, with their measurements assessed before intervention providing a baseline for post-intervention results. Clinically, our data showed that BRBs were well-tolerated with no side effects. When methylation data was combined, BRBs significantly affected methylation levels of 477 promoter regions. Pathway analysis suggests that BRB-induced intragenic hypomethylation drives leukocyte differentiation. A randomized, placebo-controlled clinical trial of BRB use in low-risk MDS or MDS/MPN patients is warranted.

Considering that presence of cancer stem cell (CSC) subpopulation in tumor tissues confers anticancer drug resistance, we investigated whether human A549 lung cancer cells resistant to etoposide possess CSC-like phenotypes. Furthermore, it is known that these malignant tumor features are the leading cause of treatment failure in cancer. We have thus attempted to explore new therapeutic agents from natural products targeting these malignancies. We found that formoxanthone C (XanX), a 1,3,5,6-tetraoxygenated xanthone from Cratoxylum formosum ssp. pruniflorum, at a non-cytotoxic concentration reduced the expression of the signal transducer and activator of transcription 1 (STAT1) and histone deacetylase 4 (HDAC4) proteins, leading to inhibition of CSC-like phenotypes such as cell migration, invasion, and sphere-forming ability. Moreover, we found that treatment with STAT1 or HDAC4 small interfering RNAs significantly hindered these CSC-like phenotypes, indicating that STAT1 and HDAC4 play a role in the malignant tumor features. Taken together, our findings suggest that XanX may be a potential new therapeutic agent targeting malignant lung tumors.