Attenuation of Polycyclic Aromatic Hydrocarbon (PAH)-Induced Carcinogenesis and Tumorigenesis by Omega-3 Fatty Acids in Mice In Vivo.

Lung cancer is the leading cause of cancer death worldwide. Polycyclic aromatic hydrocarbons (PAHs) are metabolized by the cytochrome P450 (CYP)1A and 1B1 to DNA-reactive metabolites, which could lead to mutations in critical genes, eventually resulting in cancer. Omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial against cancers. In this investigation, we elucidated the mechanisms by which omega-3 fatty acids EPA and DHA will attenuate PAH-DNA adducts and lung carcinogenesis and tumorigenesis mediated by the PAHs BP and MC. Adult wild-type (WT) (A/J) mice, Cyp1a1-null, Cyp1a2-null, or Cyp1b1-null mice were exposed to PAHs benzo[a]pyrene (BP) or 3-methylcholanthrene (MC), and the effects of omega-3 fatty acid on PAH-mediated lung carcinogenesis and tumorigenesis were studied. The major findings were as follows: (i) omega-3 fatty acids significantly decreased PAH-DNA adducts in the lungs of each of the genotypes studied; (ii) decreases in PAH-DNA adduct levels by EPA/DHA was in part due to inhibition of CYP1B1; (iii) inhibition of soluble epoxide hydrolase (sEH) enhanced the EPA/DHA-mediated prevention of pulmonary carcinogenesis; and (iv) EPA/DHA attenuated PAH-mediated carcinogenesis in part by epigenetic mechanisms. Taken together, our results suggest that omega-3 fatty acids have the potential to be developed as cancer chemo-preventive agents in people.

Implication of calcium supplementations in health and diseases with special focus on colorectal cancer.

Calcium is a fundamental and integrative element and helps to ensure optimal health by regulating various physiological and pathological processes. While there is substantiated evidence confirming the beneficial effects of calcium in the treatment, management, and prevention of various health conditions, including cancer, conflicting studies are imperative to acknowledge the potential negative role of calcium supplementation. The studies on calcium supplementation showed that a specific dose can help in the maintenance of good human health, and in the control of different types of diseases, including cancer. Calcium alone and when combined with vitamin D, emerges as a promising therapeutic option for efficiently managing cancer growth, when used with chemotherapy. Combination therapy is considered a more effective approach for treating advanced types of colorectal cancer. Nevertheless, several challenges drastically influence the treatment of cancer, such as individual discrepancy, drug resistance, and stage of cancer, among others. Henceforth, novel preventive, reliable therapeutic modalities are essential to control and reduce the incidence and mortality of colorectal cancer (CRC). The calcium-sensing receptor (CaSR) plays a pivotal role in calcium homeostasis, metabolism, and regulation of oncogenesis. Numerous studies have underscored the potential of CaSR, a G protein-coupled receptor, as a potential biomarker and target for colorectal cancer prevention and treatment. The multifaceted involvement of CaSR in anti-inflammatory and anti-carcinogenic processes paves the way for its utilization in the diagnosis and management of colorectal cancer. The current review highlights the important role of supplemental calcium in overall health and disease, along with the exploration of intricate mechanisms of CaSR pathways in the management and prevention of colorectal cancer.

Melatonin and Its Role in the Epithelial-to-Mesenchymal Transition (EMT) in Cancer.

The epithelial-to-mesenchymal transition (EMT) is a cell-biological program that occurs during the progression of several physiological processes and that can also take place during pathological situations such as carcinogenesis. The EMT program consists of the sequential activation of a number of intracellular signaling pathways aimed at driving epithelial cells toward the acquisition of a series of intermediate phenotypic states arrayed along the epithelial-mesenchymal axis. These phenotypic features include changes in the motility, conformation, polarity and functionality of cancer cells, ultimately leading cells to stemness, increased invasiveness, chemo- and radioresistance and the formation of cancer metastasis. Amongst the different existing types of the EMT, type 3 is directly involved in carcinogenesis. A type 3 EMT occurs in neoplastic cells that have previously acquired genetic and epigenetic alterations, specifically affecting genes involved in promoting clonal outgrowth and invasion. Markers such as E-cadherin; N-cadherin; vimentin; and transcription factors (TFs) like Twist, Snail and ZEB are considered key molecules in the transition. The EMT process is also regulated by microRNA expression. Many miRNAs have been reported to repress EMT-TFs. Thus, Snail 1 is repressed by miR-29, miR-30a and miR-34a; miR-200b downregulates Slug; and ZEB1 and ZEB2 are repressed by miR-200 and miR-205, respectively. Occasionally, some microRNA target genes act downstream of the EMT master TFs; thus, Twist1 upregulates the levels of miR-10b. Melatonin is an endogenously produced hormone released mainly by the pineal gland. It is widely accepted that melatonin exerts oncostatic actions in a large variety of tumors, inhibiting the initiation, progression and invasion phases of tumorigenesis. The molecular mechanisms underlying these inhibitory actions are complex and involve a great number of processes. In this review, we will focus our attention on the ability of melatonin to regulate some key EMT-related markers, transcription factors and micro-RNAs, summarizing the multiple ways by which this hormone can regulate the EMT. Since melatonin has no known toxic side effects and is also known to help overcome drug resistance, it is a good candidate to be considered as an adjuvant drug to conventional cancer therapies.

Effects of probiotic supplementation on chronic inflammatory process modulation in colorectal carcinogenesis.

The current study investigated the potential effects of probiotic supplementation on colorectal carcinogenesis chemically induced with 1,2-dimethylhydrazine (DMH) and treated with 5-fluorouracil (5FU)-based chemotherapy in mice. Animals were randomly allocated in five different groups: Control: which not receive any treatment throughout the experimental course; Colitis model group (DMH): treated with DMH; DMH+ 5FU: animals received I.P. (intraperitoneal) dose of chemotherapy on a weekly basis; DMH+PROB: animals received daily administrations (via gavage) of probiotics (Lactobacillus: acidophilus and paracasei, Bifidobacterium lactis and bifidum); and DMH+ PROB+ 5FU: animals received the same treatment as the previous groups. After ten-week treatment, mice's large intestine was collected and subjected to colon length, histopathological, periodic acid-schiff (PAS) staining and immunohistochemistry (TLR2, MyD88, NF-κB, IL-6, TLR4, TRIF, IRF-3, IFN-γ, Ki-67, KRAS, p53, IL-10, and TGF-ß) analyzes. Variance (ANOVA) and Kruskal-Wallis tests were used for statistical analysis, at significance level p 0.05. Probiotics' supplementation has increased the production of Ki-67 cell-proliferation marker, reduced body weight, and colon shortening, as well as modulated the chronic inflammatory process in colorectal carcinogenesis by inhibiting NF-κB expression and mitigating mucin depletion. Thus, these findings lay a basis for guide future studies focused on probiotics' action mechanisms in tumor microenvironment which might have implications in clinical practice.

Comprehensive Review on Herbal Medicine: Emphasis on Current Therapy and Role of Phytoconstituents for Cancer Treatment.

INTRODUCTION: Cancer poses a significant public health challenge in both developed and developing nations, with a rising global incidence of patients facing the threat of death due to abnormal cell proliferation. AIM: Review explores the utilization of different parts of herbal medicinal plants and their active pharmaceutical constituents in the prevention and treatment of various types of cancer. METHODOLOGY: Various anticancer medicinal plants have been identified, demonstrating their therapeutic effects by inhibiting cancer-stimulating enzymes and hormones, activating DNA repair processes, boosting the synthesis of protective stimulants, reducing the formation of free radicals, and enhancing individual immunity. Data for this study were gathered from diverse online bibliographic and databases, including Google, Google Scholar, Mendeley, Springer Link, Research Gate, and PubMed. RESULT: Herbal drugs have a huge contribution to the inhibition of the progression of cancer.A large volume of clinical studies has reported the beneficial effects of herbal medicines on the survival, immune modulation, and quality of life (QOL) of cancer patients, when these herbal medicines are used in combination with conventional therapeutics. CONCLUSION: The latest medicines for the clinical purpose (Above 50 %) are derived from herbal products. Furthermore, combination of these herbs with nanotechnology shows promise in treating specific carcinomas.

The Garlic Compound, Diallyl Trisulfide, Attenuates Benzo[a]Pyrene-Induced Precancerous Effect through Its Antioxidant Effect, AhR Inhibition, and Increased DNA Repair in Human Breast Epithelial Cells.

Exposure to B[a]P, the most characterized polycyclic aromatic hydrocarbon, significantly increases breast cancer risk. Our lab has previously reported that diallyl trisulfide (DATS), a garlic organosulfur compound (OSC) with chemopreventive and cell cycle arrest properties, reduces lipid peroxides and DNA damage in normal breast epithelial (MCF-10A) cells. In this study, we evaluated the ability of DATS to block the B[a]P-induced initiation of carcinogenesis in MCF-10A cells by examining changes in proliferation, clonogenic formation, reactive oxygen species (ROS) formation, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, and protein expression of ARNT/HIF-1ß, CYP1A1, and DNA POLß. The study results indicate that B[a]P increased proliferation, clonogenic formation, ROS formation, and 8-OHdG levels, as well as increasing the protein expression of ARNT/HIF-1ß and CYP1A1 compared to the control. Conversely, DATS/B[a]P co-treatment (CoTx) inhibited cell proliferation, clonogenic formation, ROS formation, and 8-OHdG levels compared to B[a]P alone. Treatment with DATS significantly inhibited (p < 0.0001) AhR expression, implicated in the development and progression of breast cancer. The CoTx also attenuated all the above-mentioned B[a]P-induced changes in protein expression. At the same time, it increased DNA POLß protein expression, which indicates increased DNA repair, thus causing a chemopreventive effect. These results provide evidence for the chemopreventive effects of DATS in breast cancer prevention.

Frequency of skin cancer among psoriasis, vitiligo, and mycosis fungoides patients treated with narrowband ultraviolet B phototherapy.

BACKGROUND: Narrowband ultraviolet B (NB-UVB) phototherapy is a popular and relatively contemporary treatment option. However, only a few studies to date have explored the potential risk of skin cancer following NB-UVB treatment. OBJECTIVE: This study aimed to investigate the potential long-term risk of skin cancer in patients treated with NB-UVB. METHODS: This cohort study included patients with psoriasis, vitiligo, and mycosis fungoides treated with NB-UVB at two university hospitals in Israel in 2000-2005. Patients were followed up for skin cancer for at least 10 years. Data were extracted from the hospital and community medical records. RESULTS: A total of 767 patients were included in this study: 509 with psoriasis, 122 with vitiligo, and 136 with mycosis fungoides. The mean follow-up duration was 13 years. Among these patients, 4.43% developed skin cancer during the follow-up (3.93% had psoriasis, 2.46% had vitiligo, and 8.09% had mycosis fungoides). Old age and fair skin type were the only significant independent risk factors for skin cancer. There was no significant difference in the mean number of NB-UVB treatments among patients who developed skin cancer and those who did not (99.09 vs. 94.79, respectively). CONCLUSION: No association was observed between the number of NB-UVB treatments and carcinogenesis in any study group. Age is a significant risk factor, and older patients treated with NB-UVB should be followed up carefully.

Huangqin Decoction Delays Progress of Colitis-Associated Carcinogenesis by Regulating Nrf2/HO-1 Antioxidant Signal Pathway in Mice.

OBJECTIVE: To investigate the effect of Huangqin Decoction (HQD) on nuclear factor erythroid 2 related-factor 2 (Nrf2)/heme oxygenase (HO-1) signaling pathway by inducing the colitis-associated carcinogenesis (CAC) model mice with azoxymethane (AOM)/dextran sodium sulfate (DSS). METHODS: The chemical components of HQD were analyzed by liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS/MS) to determine the molecular constituents of HQD. Totally 48 C57BL/6J mice were randomly divided into 6 groups by a random number table, including control, model (AOM/DSS), mesalazine (MS), low-, medium-, and high-dose HQD (HQD-L, HQD-M, and HQD-H) groups, 8 mice in each group. Except for the control group, the mice in the other groups were intraperitoneally injected with AOM (10 mg/kg) and administrated with 2.5% DSS orally for 1 week every two weeks (totally 3 rounds of DSS) to construct a colitis-associated carcinogenesis mouse model. The mice in the HQD-L, HQD-M and HQD-H groups were given HQD by gavage at doses of 2.925, 5.85, and 11.7 g/kg, respectively; the mice in the MS group was given a suspension of MS at a dose of 0.043 g/kg (totally 11 weeks). The serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured by enzyme-linked immunosorbent assay. The mRNA and protein expression levels of Nrf2, HO-1, and inhibitory KELCH like ECH-related protein 1 (Keap1) in colon tissue were detected by quantitative real-time PCR, immunohistochemistry, and Western blot, respectively. RESULTS: LC-Q-TOF-MS/MS analysis revealed that the chemical constituents of HQD include baicalin, paeoniflorin, and glycyrrhizic acid. Compared to the control group, significantly higher MDA levels and lower SOD levels were observed in the model group (P<0.05), whereas the expressions of Nrf2 and HO-1 were significantly decreased, and the expression of Keap1 increased (P<0.01). Compared with the model group, serum MDA level was decreased and SOD level was increased in the HQD-M, HQD-H and MS groups (P<0.05). Higher expressions of Nrf2 and HO-1 were observed in the HQD groups. CONCLUSION: HQD may regulate the expression of Nrf2 and HO-1 in colon tissue, reduce the expression of MDA and increase the expression of SOD in serum, thus delaying the progress of CAC in AOM/DSS mice.

The impact of gut bacteria producing long chain homologs of vitamin K2 on colorectal carcinogenesis.

Colorectal cancer (CRC) is one of the foremost causes of cancer-related deaths. Lately, a close connection between the course of CRC and the intestinal microbiota has been revealed. Vitamin K2 (VK2) is a bacterially derived compound that plays a crucial role in the human body. Its significant anti-cancer properties may result, inter alia, from a quinone ring possessing a specific chemical structure found in many chemotherapeutics. VK2 can be supplied to our body exogenously, i.e., through dietary supplements or fermented food (e.g., yellow cheese, fermented soybeans -Natto), and endogenously, i.e., through the production of bacteria that constantly colonize the human microbiome of the large intestine.This paper focuses on endogenous K2 synthesized by the most active members of the human gut microbiome. This analysis tested 86 intestinally derived bacterial strains, among which the largest VK2 producers (Lactobacillus, Bifidobacterium, Bacillus) were selected. Moreover, based on the chosen VK2-MK4 homolog, the potential of VK2 penetration into Caco-2 cells in an aqueous environment without the coexistence of fats, pancreatic enzymes, or bile salts has been displayed. The influence of three VK2 homologs: VK2-MK4, VK2-MK7 and VK2-MK9 on apoptosis and necrosis of Caco-2 cells was tested proving the lack of their harmful effects on the tested cells. Moreover, the unique role of long-chain homologs (VK2-MK9 and VK2-MK7) in inhibiting the secretion of pro-inflammatory cytokines such as IL-8 (for Caco-2 tissue) and IL-6 and TNFα (for RAW 264.7) has been documented.

Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review.

This review delves into the intricate relationship between excess folate (vitamin B9) intake, especially its synthetic form, namely, folic acid, and its implications on health and disease. While folate plays a pivotal role in the one-carbon cycle, which is essential for DNA synthesis, repair, and methylation, concerns arise about its excessive intake. The literature underscores potential deleterious effects, such as an increased risk of carcinogenesis; disruption in DNA methylation; and impacts on embryogenesis, pregnancy outcomes, neurodevelopment, and disease risk. Notably, these consequences stretch beyond the immediate effects, potentially influencing future generations through epigenetic reprogramming. The molecular mechanisms underlying these effects were examined, including altered one-carbon metabolism, the accumulation of unmetabolized folic acid, vitamin-B12-dependent mechanisms, altered methylation patterns, and interactions with critical receptors and signaling pathways. Furthermore, differences in the effects and mechanisms mediated by folic acid compared with natural folate are highlighted. Given the widespread folic acid supplementation, it is imperative to further research its optimal intake levels and the molecular pathways impacted by its excessive intake, ensuring the health and well-being of the global population.

Recent Progress in Nanotechnology Improving the Therapeutic Potential of Polyphenols for Cancer.

Polyphenols derived from fruits, vegetables, and plants are bioactive compounds potentially beneficial to human health. Notably, compounds such as quercetin, curcumin, epigallocatechin-3-gallate (EGCG), and resveratrol have been highlighted as antiproliferative agents for cancer. Due to their low solubility and limited bioavailability, some alternative nanotechnologies have been applied to encapsulate these compounds, aiming to improve their efficacy against cancer. In this comprehensive review, we evaluate the main nanotechnology approaches to improve the therapeutic potential of polyphenols against cancer using in vitro studies and in vivo preclinical models, highlighting recent advancements in the field. It was found that polymeric nanomaterials, lipid-based nanomaterials, inorganic nanomaterials, and carbon-based nanomaterials are the most used classes of nanocarriers for encapsulating polyphenols. These delivery systems exhibit enhanced antitumor activity and pro-apoptotic effects, particularly against breast, lung, prostate, cervical, and colorectal cancer cells, surpassing the performance of free bioactive compounds. Preclinical trials in xenograft animal models have revealed decreased tumor growth after treatment with polyphenol-loaded delivery systems. Moreover, the interaction of polyphenol co-delivery systems and polyphenol-drug delivery systems is a promising approach to increase anticancer activity and decrease chemotherapy side effects. These innovative approaches hold significant implications for the advancement of clinical cancer research.

Opportunities and Challenges of Kava in Lung Cancer Prevention.

Lung cancer is the leading cause of cancer-related deaths due to its high incidence, late diagnosis, and limited success in clinical treatment. Prevention therefore is critical to help improve lung cancer management. Although tobacco control and tobacco cessation are effective strategies for lung cancer prevention, the numbers of current and former smokers in the USA and globally are not expected to decrease significantly in the near future. Chemoprevention and interception are needed to help high-risk individuals reduce their lung cancer risk or delay lung cancer development. This article will review the epidemiological data, pre-clinical animal data, and limited clinical data that support the potential of kava in reducing human lung cancer risk via its holistic polypharmacological effects. To facilitate its future clinical translation, advanced knowledge is needed with respect to its mechanisms of action and the development of mechanism-based non-invasive biomarkers in addition to safety and efficacy in more clinically relevant animal models.

Phototherapy and DNA Damage: A Systematic Review.

Phototherapy has gained popularity in the recent decades for the treatment of various immune-mediated dermatological conditions since it is more-cost effective and less toxic compared to systemic therapies. This systematic review aims to inform dermatology providers of the risks and benefits of phototherapy, especially in patients at risk for malignancies. Ionizing energy from phototherapy results in DNA photolesions, namely of cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs). Without adequate repair, these mutations increase the risk for carcinogenesis. Additionally, phototherapy can also indirectly cause DNA damage through the formation of reactive oxygen species (ROS), which damage of several structural and functional proteins and DNA. When choosing a phototherapy modality, it also important to take into consideration the side effect profiles associated with each modality. For instance, a 10-fold higher dose of NB-UVB is required to produce a similar amount of CPDs compared with BB-UVB. Patients who undergo UVA with psoralen (PUVA) can be susceptible to developing skin malignancies up to 25 years after receiving their last treatment. It would behoove providers to consider optimal radiation dosage given each patients' level of skin pigmentation and potential for photoadaptation. Additionally, there are measures have been proposed to minimize deleterious skin changes, such as a 42-degree Celsius heat treatment using a 308nm excimer laser prior to UVB phototherapy and low frequency, low intensity electromagnetic fields along with UVB. However, as performing routine skin exams, remain paramount in the prevention of phototherapy-induced neoplasia.

C-type natriuretic peptide (CNP) inhibits 7,12-Dimethylbenz[a]anthracene (DMBA)/Croton oil-induced skin tumor growth by modulating inflammation in Swiss albino mice.

C-type natriuretic peptide (CNP) exhibits anti-inflammatory activity besides its natriuretic and diuretic functions. The present study aimed to determine the anticancer and synergistic therapeutic activity of CNP against a 7,12-Dimethylbenz[a]anthracene (DMBA)/Croton oil-induced skin tumor mouse model. CNP (2.5 µg/kg body weight) was injected either alone and/or in combination with Cisplatin (CDDP) (2 mg/kg body weight) for 4 weeks. The dorsal skin tumor incidences/growth and mortality rate were recorded during the experimental period of 16 weeks. The serum C-reactive protein (CRP), and lactate dehydrogenase (LDH) levels, infiltrating mast cells, and AgNORs proliferating cells count were analyzed in control and experimental mice. Further, the expression profile of marker genes of proliferation, inflammation, and progression molecules were analyzed using Reverse transcriptase-polymerase chain reaction (RT-PCR)/quantitative PCR (qPCR), western blot, and immunohistochemistry. The DMBA/Croton oil-induced mice exhibited 100% tumor incidence. Whereas, CNP alone, CDDP alone, and CNP+CDDP combination-treated mice exhibited 58%, 46%, and 24% tumor incidence, respectively. Also, a marked reduction in the levels of serum CRP and LDH, the number of infiltrating mast cells count and AgNORs proliferating cells count were noticed in the mice skin sections. Further, a significant reduction in both mRNA and protein expression levels of proliferation, inflammation, and progression markers were noticed in CNP (p < 0.01), CDDP (p < 0.01), and CNP+CDDP combination (p < 0.001) treated mice, respectively. The results of the present study suggest that CNP has anticancer activity. Further, the CNP+CDDP treatment has more promising anticancer activity as compared with CNP or CDDP alone treatment, probably due to the synergistic antiproliferative and anti-inflammatory activities of CNP and CDDP.

Sanwu Baisan decoction inhibits colorectal cancer progression in mice by remodeling gut microbiota and tumorigenesis.

OBJECTIVE: To uncover the anti-tumor effects and potential mechanism of Sanwu Baisan Decoction (, SWB) in treatment of colorectal cancer (CRC) in mice. METHODS: Therapeutic effect was evaluated based on body weight gain, tumor volume, tumor growth inhibition rate, and histological changes and apoptosis in the tumor tissues. Anti-tumor immunity was studied by measuring plasma levels of anti-tumor cytokines, interleukin 6 (IL-6), interleukin 17 (IL-17), and interferon γ (IFN-γ). Gut morphological changes were evaluated by histological staining and tight junction proteins expressions. Gut microbiota composition was analyzed by 16S rRNA gene sequencing. Classical toll-like receptor 4 (TLR-4)/ cyclooxygenase 2 (COX-2)/ prostaglandin E2 (PGE-2) pathway was examined in colon tissue and tumor samples. RESULTS: SWB presented high anti-tumor efficacy of CRC in mice, which manifested as decreased tumor volume and increased tumor growth inhibition rate. This anti-tumor effect of SWB was associated with elevated plasma levels of anti-tumor immune cytokines (IL-6, IL-17, and IFN-γ). Further studies showed that SWB also increases the expression of occluding and promotes the abundance of gut probiotics, , , and . Moreover, results suggested that the anti-tumor effects of SWB might associate with inducing cancer cell apoptosis and inhibiting the TLR-4/COX-2/PGE-2 pathway in both colon tissue and tumor samples. CONCLUSION: SWB shows strong anti-tumor efficiency in mice with colorectal carcinoma, possibly through promoting the secretion of anti-tumor immune cytokines, inducing cancer apoptosis, maintaining the gut microbiota, and inhibiting tumorigenesis by inhibiting the TLR-4/COX-2/PGE-2 pathway.

Associations of the 2018 World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) cancer prevention recommendations with stages of colorectal carcinogenesis.

BACKGROUND: While adherence to cancer prevention recommendations is linked to lower risk of colorectal cancer (CRC), few have studied associations across the entire spectrum of colorectal carcinogenesis. Here, we studied the relationship of the standardized 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score for cancer prevention recommendations with detection of colorectal lesions in a screening setting. As a secondary objective, we examined to what extent the recommendations were being followed in an external cohort of CRC patients. METHODS: Adherence to the seven-point 2018 WCRF/AICR Score was measured in screening participants receiving a positive fecal immunochemical test and in CRC patients participating in an intervention study. Dietary intake, body fatness and physical activity were assessed using self-administered questionnaires. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for screen-detected lesions. RESULTS: Of 1486 screening participants, 548 were free from adenomas, 524 had non-advanced adenomas, 349 had advanced lesions and 65 had CRC. Adherence to the 2018 WCRF/AICR Score was inversely associated with advanced lesions; OR 0.82 (95% CI 0.71, 0.94) per score point, but not with CRC. Of the seven individual components included in the score, alcohol, and BMI seemed to be the most influential. Of the 430 CRC patients included in the external cohort, the greatest potential for lifestyle improvement was seen for the recommendations concerning alcohol and red and processed meat, where 10% and 2% fully adhered, respectively. CONCLUSIONS: Adherence to the 2018 WCRF/AICR Score was associated with lower probability of screen-detected advanced precancerous lesions, but not CRC. Although some components of the score seemed to be more influential than others (i.e., alcohol and BMI), taking a holistic approach to cancer prevention is likely the best way to prevent the occurrence of precancerous colorectal lesions.

Antioxidant and Anti-Tumor Effects of Dietary Vitamins A, C, and E.

Oxidative stress, a condition characterized by an imbalance between pro-oxidant molecules and antioxidant defense systems, is increasingly recognized as a key contributor to cancer development. This is because the reactive oxygen species (ROS) generated during oxidative stress can damage DNA, proteins, and lipids to facilitate mutations and other cellular changes that promote cancer growth. Antioxidant supplementation is a potential strategy for decreasing cancer incidence; by reducing oxidative stress, DNA damage and other deleterious cellular changes may be attenuated. Several clinical trials have been conducted to investigate the role of antioxidant supplements in cancer prevention. Some studies have found that antioxidant supplements, such as vitamin A, vitamin C, and vitamin E, can reduce the risk of certain types of cancer. On the other hand, some studies posit an increased risk of cancer with antioxidant supplement use. In this review, we will provide an overview of the current understanding of the role of oxidative stress in cancer formation, as well as the potential benefits of antioxidant supplementation in cancer prevention. Additionally, we will discuss both preclinical and clinical studies highlighting the potentials and limitations of preventive antioxidant strategies.

Nutraceutical strategies for alleviation of UVB phototoxicity.

Ultraviolet B exposure to keratinocytes promotes carcinogenesis by inducing pyrimidine dimer lesions in DNA, suppressing the nucleotide excision repair mechanism required to fix them, inhibiting the apoptosis required for the elimination of initiated cells, and driving cellular proliferation. Certain nutraceuticals - most prominently spirulina, soy isoflavones, long-chain omega-3 fatty acids, the green tea catechin epigallocatechin gallate (EGCG) and Polypodium leucotomos extract - have been shown to oppose photocarcinogenesis, as well as sunburn and photoaging, in UVB-exposed hairless mice. It is proposed that spirulina provides protection in this regard via phycocyanobilin-mediated inhibition of Nox1-dependent NADPH oxidase; that soy isoflavones do so by opposing NF-κB transcriptional activity via oestrogen receptor-beta; that the benefit of eicosapentaenoic acid reflects decreased production of prostaglandin E2; and that EGCG counters UVB-mediated phototoxicity via inhibition of the epidermal growth factor receptor. The prospects for practical nutraceutical down-regulation of photocarcinogenesis, sunburn, and photoaging appear favourable.

Projected lifetime cancer risk for patients undergoing spine surgery for isthmic spondylolisthesis.

BACKGROUND CONTEXT: Radiographs, fluoroscopy, and computed tomography (CT) are increasingly utilized in the diagnosis and management of various spine pathologies. Such modalities utilize ionizing radiation, a known cause of carcinogenesis. While the radiation doses such studies confer has been investigated previously, it is less clear how such doses translate to projected cancer risks, which may be a more interpretable metric. PURPOSE: (1) Calculate the lifetime cancer risk and the relative contributions of preference-sensitive selection of imaging modalities associated with the surgical management of a common spine pathology, isthmic spondylolisthesis (IS); (2) Investigate whether the use of intraoperative CT, which is being more pervasively adopted, increases the risk of cancer. STUDY DESIGN/SETTING: Retrospective cross-sectional study carried out within a large integrated health care network. PATIENT SAMPLE: Adult patients who underwent surgical treatment of IS via lumbar fusion from January 2016 through December 2021. OUTCOME MEASURES: (1) Effective radiation dose and lifetime cancer risk associated with each exposure to ionizing radiation; (2) Difference in effective radiation dose (and lifetime cancer risk) among patients who received intraoperative CT compared to other intraoperative imaging techniques. METHODS: Baseline demographics and differences in surgical techniques were characterized. Radiation exposure data were collected from the 2-year period centered on the operative date. Projected risk of cancer from this radiation was calculated utilizing each patient's effective radiation dose in combination with age and sex. Generalized linear modeling was used to adjust for covariates when determining the comparative risk of intraoperative CT as compared to alternative imaging modalities. RESULTS: We included 151 patients in this cohort. The range in calculated cancer risk exclusively from IS management was 1.3-13 cases of cancer per 1,000 patients. During the intraoperative period, CT imaging was found to significantly increase radiation exposure as compared to alternate imaging modalities (adjusted risk difference (ARD) 12.33mSv; IQR 10.04, 14.63mSv; p<.001). For a standardized 40 to 49-year-old female, this projects to an additional 0.72 cases of cancer per 1,000. For the entire 2-year perioperative care episode, intraoperative CT as compared to other intraoperative imaging techniques was not found to increase total ionizing radiation exposure (ARD 9.49mSv; IQR -0.83, 19.81mSv; p=.072). The effect of intraoperative imaging choice was mitigated in part due to preoperative (ARD 13.1mSv, p<.001) and postoperative CTs (ARD 22.7mSv, p<.001). CONCLUSIONS: Preference-sensitive imaging decisions in the treatment of IS impart substantial cancer risk. Important drivers of radiation exposure exist in each phase of care, including intraoperative CT and/or CT scans during the perioperative period. Knowledge of these data warrant re-evaluation of current imaging protocols and suggest a need for the development of radiation-sensitive approaches to perioperative imaging.

Lay etiology concepts of cancer patients do not correlate with their usage of complementary and/or alternative medicine.

BACKGROUND: The usage of complementary and alternative medicine (CAM) is widespread among cancer patients. While reasons for and aims of using CAM have been evaluated in many studies, less is known about whether patients' concepts of how and why cancer develops has an influence on the choice of the CAM method. METHODS: We pooled the data from all studies of our working group containing questions on lay etiological concepts and CAM usage and reanalyzed them with respect to the associations between these parameters. RESULTS: The pooled dataset from 12 studies included 4792 patients. A third (1645 patients) reported using CAM. Most often used were supplements (55.9%), relaxation techniques (43.6%), and homeopathy (37.9%). Regarding perceived causes, patients most often marked stress (35.4%) followed by genes (31.9%). While all lay etiological beliefs were highly significantly associated with usage of CAM in general, there was no association between single lay etiological concepts and types of CAM used. Yet, in a network analysis, we found two associations: one comprising trauma, mistletoe, genes, and nutritional supplements, the other yoga, vitamin C, nutritional supplements, and TCM herbs. In the correlation heatmap, one cluster comprises etiological concepts of personality, immune system and trauma, and two clusters of CAM methods emerged: one comprising praying, yoga, meditation, and relaxation procedures, the other nutritional supplements, selenium, vitamins A and C. CONCLUSION: While physicians are trained to derive treatment strategies from etiological concepts, lay people choosing CAM do not follow these rules, which may point to other needs of patients addressed by CAM.