Cancer Development Research Articles

Non-improvement of atrophic gastritis in cases of gastric cancer after successful Helicobacter pylori eradication therapy

BACKGROUND Helicobacter pylori (H. pylori) infection is closely related to the development of gastric cancer (GC). However, GC can develop even after H. pylori eradication. Therefore, it would be extremely useful if GC could be predicted after eradication. The Kyoto classification score for gastritis (GA) is closely related to cancer risk. However, how the score for GC changes after eradication before onset is not well understood. AIM To investigate the characteristics of the progression of Kyoto classification scores for GC after H. pylori eradication. METHODS Eradication of H. pylori was confirmed in all patients using either the urea breath test or the stool antigen test. The Kyoto classification score of GC patients was evaluated by endoscopy at the time of event onset and three years earlier. In addition, the modified atrophy score was evaluated and compared between the GC group and the control GA group. RESULTS In total, 30 cases of early GC and 30 cases of chronic GA were evaluated. The pathology of the cancer cases was differentiated adenocarcinoma, except for one case of undifferentiated adenocarcinoma. The total score of the Kyoto classification was significantly higher in the GC group both at the time of cancer onset and three years earlier (4.97 vs 3.73, P = 0.0034; 4.2 vs 3.1, P = 0.0035, respectively). The modified atrophy score was significantly higher in the GC group both at the time of cancer onset and three years earlier and was significantly improved only in the GA group (5.3 vs 5.3, P = 0.5; 3.73 vs 3.1, P = 0.0475, respectively). CONCLUSION The course of the modified atrophy score is useful for predicting the onset of GC after eradication. Patients with severe atrophy after H. pylori eradication require careful monitoring.

The truncated AXIN1 isoform promotes hepatocellular carcinoma metastasis through SRSF9-mediated exon 9 skipping.

Axis inhibitor protein 1 (AXIN1) is a protein recognized for inhibiting tumor growth and is commonly involved in cancer development. In this study, we explored the potential molecular mechanisms that connect alternative splicing of AXIN1 to the metastasis of hepatocellular carcinoma (HCC). Transcriptome sequencing, RT‒PCR, qPCR and Western blotting were utilized to determine the expression levels of AXIN1 in human HCC tissues and HCC cells. The effects of the AXIN1 exon 9 alternative splice isoform and SRSF9 on the migration and invasion of HCC cells were assessed through wound healing and Transwell assays, respectively. The interaction between SRSF9 and AXIN1 was investigated using UV crosslink RNA immunoprecipitation, RNA pulldown, and RNA immunoprecipitation assays. Furthermore, the involvement of the AXIN1 isoform and SRSF9 in HCC metastasis was validated in a nude mouse model. AXIN1-L (exon 9 including) expression was downregulated, while AXIN1-S (exon 9 skipping) was upregulated in HCC. SRSF9 promotes the production of AXIN1-S by interacting with the sequence of exons 8 and 10 of AXIN1. AXIN1-S significantly promoted HCC cells migration and invasion by activating the Wnt pathway, while the opposite effects were observed for AXIN1-L. In vivo experiments demonstrated that AXIN1-L inhibited HCC metastasis, whereas SRSF9 promoted HCC metastasis in part by regulating the level of AXIN1-S. AXIN1, a tumor suppressor protein that targets the AXIN1/Wnt/β-catenin signaling axis, may be a promising prognostic factor and a valuable therapeutic target for HCC.

Casual associations between blood metabolites and colon cancer

BACKGROUND Limited knowledge exists regarding the casual associations linking blood metabolites and the risk of developing colorectal cancer. AIM To investigate causal associations between blood metabolites and colon cancer. METHODS The study utilized a two-sample Mendelian randomization (MR) analysis to investigate the causal impact of 486 blood metabolites on colorectal cancer. The primary method of analysis used was the inverse variance weighted model. To further validate the results several sensitivity analyses were performed, including Cochran's Q test, MR-Egger intercept test, and MR robust adjusted profile score. These additional analyses were conducted to ensure the reliability and robustness of the findings. RESULTS After rigorous selection for genetic variation, 486 blood metabolites were included in the MR analysis. We found Mannose [odds ratio (OR) = 2.09 (1.10-3.97), P = 0.024], N-acetylglycine [OR = 3.14 (1.78-5.53), P = 7.54 × 10-8], X-11593-O-methylascorbate [OR = 1.68 (1.04-2.72), P = 0.034], 1-arachidonoylglycerophosphocholine [OR = 4.23 (2.51-7.12), P = 6.35 × 10-8] and 1-arachidonoylglycerophosphoethanolamine 4 [OR = 3.99 (1.17-13.54), P = 0.027] were positively causally associated with colorectal cancer, and we also found a negative causal relationship between Tyrosine [OR = 0.08 (0.01-0.63), P = 0.014], Urate [OR = 0.25 (0.10-0.62), P = 0.003], N-acetylglycine [0.73 (0.54-0.98), P = 0.033], X-12092 [OR = 0.89 (0.81-0.99), P = 0.028], Succinylcarnitine [OR = 0.48 (0.27-0.84), P = 0.09] with colorectal cancer. A series of sensitivity analyses were performed to confirm the rigidity of the results. CONCLUSION This study showed a causal relationship between 10 blood metabolites and colorectal cancer, of which 5 blood metabolites were found to be causal for the development of colorectal cancer and were confirmed as risk factors. The other five blood metabolites are protective factors.

Novel insights into the roles of migrasome in cancer.

Cell migration, a hallmark of cancer malignancy, plays a critical role in cancers. Improperly initiated or misdirected cell migration can lead to invasive metastatic cancer. Migrasomes are newly discovered vesicular cellular organelles produced by migrating cells and depending on cell migration. Four marker proteins [NDST1 (bifunctionalheparan sulfate N-deacetylase/N-sulfotransferase 1), EOGT (Epidermal growth factor domains pecific O-linked N-acetylglucosaminetransferase), CPQ (carboxypeptidase Q), and PIGK (phosphatidylinositol glycan anchor biosynthesis, class K)] of migrasomes were successfully identified. There are three marker proteins (NDST1, PIGK, and EOGT) of migrasome expressed in cancer. In this review, we will discuss the process of migrasome discovery, the formation of migrasome, the possible functions of migrasome, and the differences between migrasomes and exosomes, especially, the biological functions of migrasome marker proteins in cancer, and discuss some possible roles of migrasomes in cancer. We speculate that migrasomes and migracytosis can play key roles in regulating the development of cancer.

Circ_0006789 promotes cervical cancer development via the miR-615-5p/HSF1 axis.

Circular RNAs (circRNAs) are involved in the development of human cancers, including cervical cancer (CC). However, the role and mechanism of circ_0006789 (circSLC25A43) in CC are unclear. The purpose of this study was to investigate the functional role of circ_0006789 in CC. The expression of circ_0006789 in CC tissues and cell lines was examined by RT-qPCR. The characterization of circ_0006789 in CC cells was verified by subcellular localisation, actinomycin D assay, and RNase R assay. After circ_0006789 was knocked down in CC cell lines, the proliferation, apoptosis, migration and invasion of CC cells were assessed by CCK-8 method, flow cytometry, and Transwell assay. RIP assay, FISH assay, dual luciferase reporter gene assay and Western blot were used to investigate the regulatory mechanism between circ_0006789, miR-615-5p and heat shock factor 1 (HSF1). circ_0006789 was upregulated in CC tissues and cell lines. CC cells were inhibited in their proliferation, migration, and invasion, as well as promoted to apoptosis when circ_0006789 was knocked down. It was found that circ_0006789 targeted miR-615-5p, and miR-615-5p expression was inversely correlated with circ_0006789 expression. Furthermore, HSF1 was a target gene of miR-615-5p. Furthermore, the suppressive effects on HeLa cells mediated by circ_0006789 knockdown were counter-balanced when miR-615-5p was knocked down and HSF1 was overexpressed. Mechanistically, circ_0006789 was found to promote CC development by reducing miR-615-5p and increasing HSF1 expressions. circ_0006789 accelerates CC development via the miR-615-5p/HSF1 axis.

Nasal tip rotation flap for reconstruction of surgical defects on the distal nose.

The nose is a common site for the development of skin cancers. Mohs micrographic surgery (MMS) is a highly curative treatment for skin cancer of the nose. Reconstruction of MMS defects on the nose, especially on the distal aspect, can be challenging given the proximity of multiple subunits and limited adjacent tissue reservoirs. Our goal was to describe our experience using a nasal tip rotation flap (NTRF) for MMS defects on the distal nose. A retrospective review of all MMS cases at multiple institutions between June 2018 and June 2022 was undertaken. Cases that used an NTRF to repair the MMS defect(s) were selected, and data were collected on patient demographics, tumor type, anatomical location of the tumor, preoperative and postoperative size, number of stages needed to clear the tumor, repair dimensions, and any postoperative complications. A total of 66 cases that utilized an NTRF for reconstruction were included. The mean preoperative tumor size was 0.8 cm (range: 0.3-1.6 cm), and the mean defect size was 1.2 cm (range: 0.7-1.9 cm). The defects were most commonly on the nasal tip. There were no significant complications observed. The nasal tip rotation flap is a reliable reconstruction option for MMS defects of the distal nose. This flap can be used for defects that involve the nasal tip, soft triangle, and/or portions of the ala, including the alar rim.

Brevilin A Inhibits Prostate Cancer Progression by Decreasing PAX5-Activated SOX4.

Brevilin A possesses inhibitory effects on the development of prostate cancer (PCa); however, the underlying mechanism remains unclear. The present work aims to analyze how Brevilin A regulates PCa cell malignancy. RNA expression of paired box 5 (PAX5) and SRY-box transcription factor 4 (SOX4) was analyzed by quantitative real-time polymerase chain reaction. Protein expression of PAX5, SOX4, and nuclear proliferation marker (Ki67) was detected by western blotting or immunohistochemistry assay. The viability, proliferation, apoptosis, and migratory and invasive abilities of PCa cells were investigated by cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), flow cytometry, and transwell assays, respectively. The association between PAX5 and SOX4 was identified by dual-luciferase reporter assay and chromatin immunoprecipitation assay. Xenograft mouse model assay was used to reveal the effect of Brevilin A on tumor tumorigenesis in vivo. PAX5 and SOX4 expression were upregulated in PCa tissues and cells relative to normal prostate tissues and human prostate epithelial cells. Brevilin A treatment inhibited PAX5 protein expression in PCa cells. Additionally, Brevilin A inhibited proliferation, migration and invasion and induced apoptosis of PCa cells, whereas these effects were attenuated after PAX5 overexpression. SOX4 was transcriptionally activated by PAX5, and its introduction partially relieved the inhibitory effects of PAX5 knockdown on PCa cell malignancy. Moreover, Brevilin A delayed tumor formation in vivo. Brevilin A inhibited PCa progression by regulating SOX4 expression in a PAX5-dependent manner, providing a promising anti-tumor drug for PCa.

Evolution of the Innovative Therapies for Children With Cancer Consortium Trial Portfolio for Drug Development for Children With Cancer.

The aim of the Innovative Therapies for Children with Cancer (ITCC) consortium is to improve access to novel therapies for children and adolescents with cancer. The evolution of the ITCC clinical trial portfolio since 2003 was reviewed. All ITCC-labeled phase I/II trials opened between January 1, 2003 and February 3, 2018 were analyzed in two periods (2003-2010 and 2011-2018), and data were extracted from the ITCC database, regulatory agencies' registries, and publications. Sixty-one trials (62% industry-sponsored) enrolled 3,198 patients. The number of trials in the second period increased by almost 300% (16 v 45). All biomarker-driven trials (n = 14) were conducted in the second period. The use of rolling six and model-based designs increased (1 of 9, 11% v 21 of 31, 68%), and that of 3 + 3 designs decreased (5 of 9, 55% v 5 of 31, 16%; P = .014). The proportion of studies evaluating chemotherapeutics only decreased (5 of 16, 31% v 4 of 45, 9%), the proportion of single-agent targeted therapies did not change (9 of 16, 56.2% v 24 of 45, 53.3%), the proportion of combination targeted therapies trials increased (2 of 16, 12%, v 17 of 45, 38%), the proportion of randomized phase II trials increased (1 of 7, 14% v 8 of 14, 57%). More trials were part of a pediatric investigation plan in the second period (4 of 16, 25% v 21 of 45, 46%). The median time for Ethics Committees' approvals was 1.7 times longer for academic compared with industry-sponsored trials. This study reports a shift in the paradigm of early drug development for childhood cancers, with more biologically relevant targets evaluated in biomarker-driven trials or in combination with other therapies and with more model-based or randomized designs and a greater focus on fulfilling regulatory requirements. Improvement of trial setup and recruitment could increase the number of patients benefiting from novel agents.

Exploring the intricate relationship between miRNA dysregulation and breast cancer development: insights into the impact of environmental chemicals

Exploring the intricate relationship between miRNA dysregulation and breast cancer development: insights into the impact of environmental chemicals

Rhein suppresses esophageal cancer development by regulating cell cycle through DNMT3B gene.

The mechanism by which DNMT3B facilitates esophageal cancer (ESCA) progression is currently unknown, despite its association with adverse prognoses in several cancer types. To investigate the potential therapeutic effects of the Chinese herbal medicine rhubarb on esophageal cancer (ESCA), we adopted an integrated bioinformatics approach. Gene Set Enrichment Analysis (GSEA) was first utilized to screen active anti-ESCA components in rhubarb. We then employed Weighted Gene Co-expression Network Analysis (WGCNA) to identify key molecular modules and targets related to the active components and ESCA pathogenesis. This system-level strategy integrating multi-omics data provides a powerful means to unravel the molecular mechanisms underlying the anticancer activities of natural products, like rhubarb. To investigate module gene functional enrichment, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. In addition, we evaluated the predictive impact of DNMT3B expression on ESCA patients utilizing the Kaplan-Meier method. Finally, we conducted experiments on cell proliferation and the cell cycle to explore the biological roles of DNMT3B. In this study, we identified Rhein as the main active ingredient of rhubarb that exhibited significant anti-ESCA activity. Rhein markedly suppressed ESCA cell proliferation. Utilizing Weighted Gene Co-expression Network Analysis (WGCNA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we determined that the blue module was associated with Rhein target genes and the cell cycle. Additionally, DNMT3B was identified as a Rhein target gene. Analysis of The Cancer Genome Atlas (TCGA) database revealed that higher DNMT3B levels were associated with poor prognosis in ESCA patients. Furthermore, Rhein partially reversed the overexpression of DNMT3B to inhibit ESCA cell proliferation. In vitro studies demonstrated that Rhein and DNMT3B inhibition disrupted the S phase of the cell cycle and affected the production of cell cycle-related proteins. In this study, we found that Rhein exerts its anti-proliferative effects in ESCA cells by targeting DNMT3B and regulating the cell cycle.

The Transformative Role of 3D Culture Models in Triple-Negative Breast Cancer Research

Advancements in cell culturing techniques have allowed the development of three-dimensional (3D) cell culture models sourced directly from patients’ tissues and tumors, faithfully replicating the native tissue environment. These models provide a more clinically relevant platform for studying disease progression and treatment responses compared to traditional two-dimensional (2D) models. Patient-derived organoids (PDOs) and patient-derived xenograft organoids (PDXOs) emerge as innovative 3D cancer models capable of accurately mimicking the tumor’s unique features, enhancing our understanding of tumor complexities, and predicting clinical outcomes. Triple-negative breast cancer (TNBC) poses significant clinical challenges due to its aggressive nature, propensity for early metastasis, and limited treatment options. TNBC PDOs and PDXOs have significantly contributed to the comprehension of TNBC, providing novel insights into its underlying mechanism and identifying potential therapeutic targets. This review explores the transformative role of various 3D cancer models in elucidating TNBC pathogenesis and guiding novel therapeutic strategies. It also provides an overview of diverse 3D cell culture models, derived from cell lines and tumors, highlighting their advantages and culturing challenges. Finally, it delves into live-cell imaging techniques, endpoint assays, and alternative cell culture media and methodologies, such as scaffold-free and scaffold-based systems, essential for advancing 3D cancer model research and development.

FOXP4-mediated induction of PTK7 activates the Wnt/β-catenin pathway and promotes ovarian cancer development

Ovarian cancer (OV) poses a significant challenge in clinical settings due to its difficulty in early diagnosis and treatment resistance. FOXP4, belonging to the FOXP subfamily, plays a pivotal role in various biological processes including cancer, cell cycle regulation, and embryonic development. However, the specific role and importance of FOXP4 in OV have remained unclear. Our research showed that FOXP4 is highly expressed in OV tissues, with its elevated levels correlating with poor prognosis. We further explored FOXP4’s function through RNA sequencing and functional analysis in FOXP4-deficient cells, revealing its critical role in activating the Wnt signaling pathway. This activation exacerbates the malignant phenotype in OV. Mechanistically, FOXP4 directly induces the expression of protein tyrosine kinase 7 (PTK7), a Wnt-binding receptor tyrosine pseudokinase, which causes abnormal activation of the Wnt signaling pathway. Disrupting the FOXP4-Wnt feedback loop by inactivating the Wnt signaling pathway or reducing FOXP4 expression resulted in the reduction of the malignant phenotype of OV cells, while restoring PTK7 expression reversed this effect. In conclusion, our findings underscore the significance of the FOXP4-induced Wnt pathway activation in OV, suggesting the therapeutic potential of targeting this pathway in OV treatment.

Intake of oligoelements with cytarabine or etoposide alters dopamine levels and oxidative damage in rat brain

Research on the relationships between oligoelements (OE) and the development of cancer or its prevention is a field that is gaining increasing relevance. The aim was to evaluate OE and their interactions with oncology treatments (cytarabine or etoposide) to determine the effects of this combination on biogenic amines and oxidative stress biomarkers in the brain regions of young Wistar rats. Dopamine (DA), 5-Hydroxyindoleacetic acid (5-Hiaa), Glutathione (Gsh), Tiobarbituric acid reactive substances (TBARS) and Ca+2, Mg+2 ATPase enzyme activity were measured in brain regions tissues using spectrophometric and fluorometric methods previously validated. The combination of oligoelements and cytarabine increased dopamine in the striatum but decreased it in cerebellum/medulla-oblongata, whereas the combination of oligoelements and etoposide reduced lipid peroxidation. These results suggest that supplementation with oligoelements modifies the effects of cytarabine and etoposide by redox pathways, and may become promising therapeutic targets in patients with cancer.

Association of adipose tissue mediators with the development of cancer in patients with metabolic syndrome

The aim of the study was to summarize the available data on the relationship between adipose tissue mediators and cancer in patients with metabolic syndrome. Material and methods. A literature search was conducted using the PubMed and eliBRARY databases. Of the 400 articles published over the past 20 years, 58 studies were included in the review. Results. There is evidence of an unfavorable course of cancer in patients with metabolic syndrome that is explained by the presence of common pathogenetic pathways. In this review, special attention is paid to adipose tissue mediators that regulate the course of inflammation. The involvement of adipose tissue mediators in the pathogenesis of cancer is discussed. The relationship between adipokines of adipose tissue and the effects of specialized pro-resolving mediators (SpRM), which are metabolites of polyunsaturated fatty acids (resolvins, protectins and maresins), are considered. the associations of mediators that regulate the intensity of inflammation with the metabolic syndrome and cancer are discussed. Conclusion. Further studies will contribute to a better understanding of the relationship between metabolic syndrome and cancer and the search for adequate predictive markers to select the most effective drug strategy for correcting metabolic syndrome.

From genetic mosaicism to tumorigenesis through indirect genetic effects.

Genetic mosaicism has long been linked to aging, and several hypotheses have been proposed to explain the potential connections between mosaicism and susceptibility to cancer. It has been proposed that mosaicism may disrupt tissue homeostasis by affecting intercellular communications and releasing microenvironmental constraints within tissues. The underlying mechanisms driving these tissue-level influences remain unidentified, however. Here, we present an evolutionary perspective on the interplay between mosaicism and cancer, suggesting that the tissue-level impacts of genetic mosaicism can be attributed to Indirect Genetic Effects (IGEs). IGEs can increase the level of cellular stochasticity and phenotypic instability among adjacent cells, thereby elevating the risk of cancer development within the tissue. Moreover, as cells experience phenotypic changes in response to challenging microenvironmental conditions, these changes can initiate a cascade of nongenetic alterations, referred to as Indirect non-Genetic Effects (InGEs), which in turn catalyze IGEs among surrounding cells. We argue that incorporating both InGEs and IGEs into our understanding of the process of oncogenic transformation could trigger a major paradigm shift in cancer research with far-reaching implications for practical applications.

ATP6V1B1 regulates ovarian cancer progression and cisplatin sensitivity through the mTOR/autophagy pathway.

Early detection and effective chemotherapy for ovarian cancer, a serious gynecological malignancy, require further progress. This study aimed to investigate the molecular mechanism of ATPase H+-Transporting V1 Subunit B1 (ATP6V1B1) in ovarian cancer development and chemoresistance. Our data show that ATP6V1B1 is upregulated in ovarian cancer and correlated with decreased progression-free survival. Gain- and loss-of-function experiments demonstrated that ATP6V1B1 promotes the proliferation, migration, and invasion of ovarian cancer cells in vitro, while ATP6V1B1 knockout inhibits tumor growth in vivo. In addition, knocking down ATP6V1B1 increases the sensitivity of ovarian cancer cells to cisplatin. Mechanistic studies showed that ATP6V1B1 regulates the activation of the mTOR/autophagy pathway. Overall, our study confirmed the oncogenic role of ATP6V1B1 in ovarian cancer and revealed that ATP6V1B1 promotes ovarian cancer progression via the mTOR/autophagy axis.

Forkhead box E1, frequently downregulted by promoter methylation, inhibits colorectal cancer cell growth and migration

Forkhead box E1 (FOXE1), also known as thyroid transcription factor 2 (TTF-2), belongs to a large family of forkhead transcription factors. It plays important roles in embryogenesis, cell growth, and differentiation. Cancer-specific FOXE1 hypermethylation events have been identified in several cancers. However, the expression and function of FOXE1 in the tumorigenesis of colorectal cancer remain still unknown. In this study, we examined FOXE1 expression and methylation in normal colon mucosa, colorectal cancer (CRC) cell lines, and primary tumors by immunohistochemistry, semi-quantitative RT-PCR, methylation-specific PCR, and bisulfite genomic sequencing. We found that FOXE1 was frequently methylated and silenced in CRC cell lines and was downregulated in CRC tissues compared with paired adjacent non-tumor tissues. Meanwhile, low FOXE1 expression was significantly correlated with lymph node metastasis and advanced TNM stages, indicating its potential as a tumor marker. Subsequently, we established colon cancer cell lines with stable FOXE1 expression to observe the biological effect on colorectal cancer, including cell growth, migration, actin cytoskeleton, and growth of human colorectal xenografts in nude mice. Ectopic expression of FOXE1 could suppress tumor cell growth and migration and affect the organization of the actin cytoskeleton together with suppressing tumorigenicity in vivo. FOXE1 methylation was frequently seen in association with a complete absence of or downregulated gene expression, and FOXE1 plays a suppressive role in the development and progression of colorectal cancer.

Exposure to polycyclic aromatic hydrocarbons promotes the progression of low-grade cervical intraepithelial neoplasia: A population-based cohort study in China.

Low-grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high-risk human papillomavirus (HR-HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community-based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed-up at 6, 12, and 24 months, post-diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1-hydroxipayrene (1-OHP) level. Our results showed that the 1-OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P < .05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24-2.67), (1.98, 1.42-2.75), and (2.37, 1.61-3.49) at 6, 12, and 24 months, post-diagnosis, respectively. The effect was enhanced with HR-HPV positivity, as determined at 6 (1.82, 1.24-2.67), 12 (3.02, 1.74-5.23), and 24 (2.51, 1.48-4.26) months, post-diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR-HPV-positive patients than in HR-HPV-negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR-HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia.

Development and assessment of an RNA editing-based risk model for the prognosis of cervical cancer patients.

RNA editing, as an epigenetic mechanism, exhibits a strong correlation with the occurrence and development of cancers. Nevertheless, few studies have been conducted to investigate the impact of RNA editing on cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). In order to study the connection between RNA editing and CESC patients' prognoses, we obtained CESC-related information from The Cancer Genome Atlas (TCGA) database and randomly allocated the patients into the training group or testing group. An RNA editing-based risk model for CESC patients was established by Cox regression analysis and least absolute shrinkage and selection operator (LASSO). According to the median score generated by this RNA editing-based risk model, patients were categorized into subgroups with high and low risks. We further constructed the nomogram by risk scores and clinical characteristics and analyzed the impact of RNA editing levels on host gene expression levels and adenosine deaminase acting on RNA. Finally, we also compared the biological functions and pathways of differentially expressed genes (DEGs) between different subgroups by enrichment analysis. In this risk model, we screened out 6 RNA editing sites with significant prognostic value. The constructed nomogram performed well in forecasting patients' prognoses. Furthermore, the level of RNA editing at the prognostic site exhibited a strong correlation with host gene expression. In the high-risk subgroup, we observed multiple biological functions and pathways associated with immune response, cell proliferation, and tumor progression. This study establishes an RNA editing-based risk model that helps forecast patients' prognoses and offers a new understanding of the underlying mechanism of RNA editing in CESC.

Nutraceuticals Health Benefits in Cancer

Abstract: Cancer is one of the leading causes of death worldwide, with multiple pathological components. Genetic abnormalities, infection or inflammation, poor diet, radiation exposure, work stress, and/or ingestion of toxic substances have all been associated with cancer development and progression. Early detection and treatment of cancer have been shown to increase the chances of survival and recovery and reduce the side effects of anticancer drugs. Anticancer drugs continue to cause negative side effects that negate treatment benefits in terms of hospitalization and survival. Many naturally occurring bioactive compounds are shown to have anticancer properties. That is, they can eliminate altered and cancer cells without harming their healthy counterparts. In particular, the following activities have been reported to support nutrition during cancer treatment: cell growth inhibition, antioxidant activity, anti-inflammatory activity, and minimized negative effects due to natural antioxidants. Keeping the side effects minimum helps patients adhere to anticancer therapy. Among currently available anticancer agents, dietary supplementation can be considered in conjunction with current chemotherapy to improve response and compliance in cancer patients. However, it should be noted that before discussing data from studies on bioactive plant supplements, it is important to ensure that the tests were performed according to protocol.