Premalignant Research Articles

Prevalence, Incidence and Predictors of Anal HPV Infection and HPV-Related Squamous Intraepithelial Lesions in a Cohort of People Living with HIV

Background: Anal HPV infection can cause squamous intraepithelial lesions (SILs), which are precursors of anal squamous cell carcinoma (SCC). The early detection of HPV infections and improvement of effective screening programmes are, therefore, essential to prevent progression from pre-cancerous lesions to SCC, especially in people living with HIV (PLWH), who represent a population at higher risk of HPV infection and associated lesions. Among prevention strategies, HPV vaccination is relevant too, but its efficacy in persons already infected by HPV is still debated. Methods: This is a retrospective single-center study on a cohort of PLWH who performed longitudinal screening for anal dysplasia and HPV infection. The screening included cytological and molecular analyses. Results: A total of 110 PLWH performed at least one anal HPV screening, with an overall prevalence of HPV infection of 86.4% [23.6% low risk (LR)-HPV and 62.7% high risk (HR)-HPV genotypes]. Abnormal cytology was demonstrated in 39.1% of subjects, of whom ASCUS 6.4%, LSIL 30.9% and HSIL 1.8%. In total, 80 patients (72.7%) had an available longitudinal screening. No patient developed SCC during follow-up. However, a high incidence of new cytological abnormalities and new HPV infections was observed. On the other side, clearance of some HPV genotypes was also frequent, confirming that HPV infection is a dynamic process. A CD4 cell count > 500/mmc was an independent predictor of HPV clearance. HPV vaccination was performed on 30.9% of patients. A trend toward an increased clearance of HPV genotypes included in 9-valent vaccine was observed in vaccinated patients (40.6% versus 30.8% in unvaccinated, p = 0.079). Conclusions: A high prevalence of HPV infection and SILs was observed in our cohort of PLWH. A high incidence of new HPV infections and HPV-associated lesions was also observed in the longitudinal cohort, highlighting the need of strengthening immunization programs and continuous screening for anal HPV infection. Whether HPV vaccination may be efficacious in patients already infected by HPV remains to be determined.

Multiple Myeloma Cells Shift the Fate of Cytolytic ILC2s Towards TIGIT-Mediated Cell Death

Background: Growing evidence attests to the multifaceted roles of group 2 innate lymphoid cells (ILC2s) in cancer immunity. They exhibit either pro- or anticancer activity depending on tumor type but their function in Multiple Myeloma (MM) is still not elucidated. Methods: The bone marrow (BM) and peripheral blood (PB) of patients (pts) with MM or precancerous conditions were collected, and specific properties of ILC2 subsets were assessed by flow cytometry. Results: By dissecting ILC2s according to c-Kit marker, we observed that NKp30 and NKG2D were mainly confined to c-Kithi ILC2s, while levels of DNAM-1 was significantly higher in fully mature c-Kitlo cells. Among the total MM-associated ILC2s (MM-ILC2s), we observed a significant increase in c-the Kitlo subset, but the expression of DNAM-1 in these cells was significantly reduced, especially in BM. Interestingly, MM-ILC2s from PB expressed granzyme B (GZMB), but its expression was impaired in BM-ILC2s. Accordingly, MM cells were susceptible to killing by MM-ILC2s derived from PB while eluding ILC2 surveillance in BM. Indeed, in MM-ILC2s derived from BM, the downregulation of DNAM-1 is accompanied by the upregulation of TIGIT, which mediate cell death in ILC2s upon recognition of the cognate ligands expressed by MM cells. These ILC2 changes appeared in clinical precursor conditions and eventually accumulated with disease progression. Conclusions: MM-ILC2s can act as cytolytic immune effectors that are fully competent in PB. However, MM cells shift ILC2 fate towards cell death in BM via the upregulation of TIGIT, thereby representing a potential therapeutic target to restore ILC2 antitumor activity.

Molecular Mechanisms of Magnolol in Gastric Precancerous Lesions: A Computational and Experimental Study.

The formation of gastric precancerous-lesions(GPLs) has been identified as a critical step intumorigenesis, and patients with GPLs have an increased risk of gastric cancer. Magnolol is the primary biphenolic compound inMagnolia officinalis. It possesses variouspharmacological properties, such ascardioprotective and neuroprotective properties, and inhibit tumor growth. However, its therapeutic effects on GPLstreatment and the related mechanisms have not yet been studied. To address this, the mechanisms by whichmagnolol affectsGPLswere elucidated via protein-chemical interaction predictionanalysis, molecular docking, molecular dynamics simulation, and experimental verification. GPL-related targets were obtained from the GeneCards database, whereasmagnolol targets were obtained from the STITCHdatabase. The two group of targets were compared by constructing a Venn diagram, and potential key GPL-related targets of magnolol were identified. Next, the interactions between the active compounds of magnololand epithelial-mesenchymal transition (EMT)-related proteins were evaluated via molecular docking. The protein-compound complexes with the optimal binding affinity were analysed viamolecular dynamics simulation. The efficacy and mechanismsof Magnolol in the treatment of GPLs werefurther assessed using in-vitro models. Magnolol exerts its pharmacological effects by acting on multiple targets. ERBB2 might be a potential target of magnolol in GPL treatment.

Peptide pool instability of precancerous lesions in rats with chronic pancreatitis model and/or without type 1 diabetes mellitus.

The search for early and minimally invasive diagnostic approaches to pancreatic cancer (PC) remains an important issue. One of the most promising directions is to find a sensitive key in the metabolic changes during widespread causes of PC, i.e., chronic pancreatitis (CP) and diabetes mellitus (DM). The main objective of this study was to analyze the peptide pools in the blood plasma and pancreas of rats with modeling of CP and/or without type 1 DM in association with pancreas histopathological grading features. The study was conducted on white non-linear male rats, divided into 3 groups: 1st group: control, 2nd group: rats with cerulein-stimulated CP, and 3rd group: rats with CP and streptozotocin-inducible type 1 DM. Total protein and peptide content were determined in the pancreas and blood plasma. The peptide pools were fractionated using size-exclusion chromatography. Rats with CP showed a high degree of fibrosis in the pancreas and grade 1 ductal pancreatic intraepithelial neoplasia (PanIN), associated with decreased total peptides in the pancreas. In rats with CP and DM, 2nd and 3rd grade PanIN with pronounced acinar metaplasia was observed in association with decreasing total pancreatic protein and peptide pools. While there was a decrease in total protein and an increase in total peptide in blood serum, the changes were more pronounced in rats with CP and DM. A study revealed both qualitative and quantitative differences in the distribution of peptide pools in 2 groups with pathologies. Qualitatively, plasma samples from pathological groups exhibited an increased number of peaks. Quantitatively, there was a higher proportion of peptides with molecular weights exceeding 700 Da observed in both plasma and pancreas. The analysis of peptide pools obtained from plasma and PanIN development demonstrated that the peptide pool can serve as an early and complementary indicator of PC emergence.

In situ detection of individual classical MHC-I gene products in cancer.

Tumor-specific HLA class I expression is required for cytotoxic T-cell elimination of cancer cells expressing tumor-associated or neo-antigens. Cancers downregulate antigen presentation to avoid adaptive immunity. The highly polymorphic nature of the genes encoding these proteins, coupled with quaternary-structure changes after formalin fixation, complicate detection by immunohistochemistry. In this study we determined recognition of 16 specific HLA-A, B and C alleles by 15 antibodies commercially available for immunohistochemical use, identifying and validating pan and specific HLA-A, B, and C antibodies, providing a validated method that can be applied to investigate HLA-A, B and C molecule-specific loss in cancer. We applied this approach to a series of breast cancers as a proof of utility, identifying differential HLA-A, B and C loss, with a higher incidence of HLA-A and B loss in hormone-driven breast cancers, HLA-B loss in HER2+ cancers, and an equal loss of all three molecules in triple-negative disease. Additionally, we found that at the protein level, HLA-A and B loss were early events prevalent in premalignant lesions, while HLA-C loss was less common throughout tumor evolution. Effective response to immunotherapies such as checkpoint inhibitors and MHC-I-targeted cancer vaccines, which hinge on the carriage of specific allele groups, require MHC-I expression on tumor cells. These findings have implications for the success of checkpoint inhibitors and vaccine strategies.

Neoplastic premalignant pancreatobiliary lesions: current update on the spectrum of lesions and their imaging appearances.

Common pancreatobiliary epithelial malignancies such as pancreatic ductal adenocarcinoma, cholangiocarcinoma and gallbladder carcinoma have poor prognosis. A small but significant portion of these malignancies arise from mass-forming grossly and radiologically visible premalignant epithelial neoplasms in the pancreatobiliary tree. Several lesions, including a few recently described entities, fall under this category and predominantly include papillary epithelial lesions with or without mucin production. These include common lesions such as intraductal papillary mucinous lesions (IPMN) in pancreas and less common to rare lesions such intraductal papillary neoplasms of the bile ducts (IPNB), pancreatic and biliary intraductal oncocytic papillary neoplasms (IOPN) and intraductal tubulopapillary neoplasms (ITPN), intracholecystic neoplasms (ICN) in the gallbladder, intra-ampullary papillary-tubular neoplasms (IAPN) in the ampulla and mucinous cystic neoplasms in the pancreas, biliary tree and gallbladder. These lesions have an excellent prognosis before malignant transformation and even with malignant transformation, often fare better than the conventional malignant counterparts. These lesions have characteristic histologic, radiologic, and molecular characteristic features. Several of these neoplastic lesions are associated with field-effect phenomenon which means that in presence of even one of these lesions, the entire background ductal epithelium is at risk of developing synchronous or metachronous malignancies. Awareness of these lesions and their imaging appearances as well as utilization of relevant molecular diagnostics can help practicing radiologists and clinicians improve patient outcomes by detecting early and treating or surveilling such lesions before malignant transformation or before metastatic dissemination.

Incidental focal 18F-FDG uptake in colorectal locations on PET/CT for oncologic reasons: pathologic correlation with endoscopic findings

Aims: Incidental focal 18-fluorodeoxyglucose (18F-FDG) uptake in the colorectal region on positron emission tomography/computed tomography (PET/CT) may indicate premalignant lesions, such as adenomas or malignancies. Early detection and diagnosis are crucial for cancer prevention. This study aimed to assess the characteristics of incidental focal colonic FDG uptake associated with benign, premalignant, and malignant lesions, and to determine when colonoscopy is necessary. Methods: A retrospective review of PET/CT reports was conducted on 5.380 patients with confirmed or suspected malignancies who underwent whole-body 18F-FDG PET/CT between January 2019 and April 2024. Patients exhibiting focal colonic 18F-FDG uptake and subsequently referred for colonoscopy were included in this study. Results: Among 110 patients who underwent colonoscopy, 63 (57.3%) had adenomas and 14 (12.7%) had malignant tumors. The receiver operating characteristic (ROC) curve based on the maximum standardized uptake value (SUVmax) showed an AUC of 0.958. A cutoff value of 13.80 was optimal for distinguishing malignant lesions from nonmalignant lesions, with a sensitivity of 92%, specificity of 89%, positive predictive value of 56%, and negative predictive value of 98%. The SUVmax significantly differentiated malignancy from other colonoscopic findings (p0.05). Conclusion: The colonoscopy results indicated that malignant lesions had significantly elevated SUVmax values compared to other lesion types or physiological uptake. However, the SUVmax was not sufficient to distinguish benign lesions from adenomas. Therefore, all incidental colonic findings should be thoroughly assessed, and lesions with SUVmax ≥13.80 should be promptly evaluated.

Research progress of DNA methylation in the screening of cervical cancer and precancerous lesions

AbstractCervical cancer is one of the most common malignant tumors that seriously threaten women's health. Persistent infection with high risk human papillomavirus (HPV) is closely related to the progression of cervical cancer. Cervical cancer screening is an effective measure to reduce the incidence and mortality of cervical cancer. The two most common screening strategies are cytology and HPV testing, but they easily lead to missed diagnosis or overdiagnosis. To overcome such limitations, a new triage method needs to be explored. The World Health Organization second edition guideline includes DNA methylation testing as a new method to be evaluated. DNA methylation is a common epigenetic modification and is considered to be closely related to the occurrence and development of tumors. In recent years, many methylated genes have been found to be biomarkers for cervical cancer and precancerous lesions diagnosis. In this paper, we focus on the role and application of host DNA methylation, HPV DNA methylation, as well as combined host and HPV DNA methylation in the screening of cervical cancer and precancerous lesions.

Smoking-induced shifts in salivary exosomal cytokines and amino acid profiles as potential early biomarkers for oral cancer.

Chronic smoking is an established risk factor for oral cancer (OC). The role of tobacco in oral squamous cell cancer (OSCC) emphasizes the need for non-invasive diagnostic approaches to identify early molecular alterations and improve patient outcomes. Salivary exosomes, which contain proteins, lipids, and nucleic acids, accessible and rich in biological content, making them interesting candidate biomarkers. Saliva samples were collected from non-smokers (n=20), smokers (n=20), and patients with oral cancer (n=20). Salivary exosomes were isolated and characterized using various techniques, including estimation of protein concentrations and amino acid profiling using High-Performance Liquid Chromatography (HPLC). Fourier Transform Infrared (FTIR) spectroscopy analyzed protein and amino acid peaks, while enzyme-linked immunosorbent assay (ELISA) measured pro-inflammatory cytokines IL-6 and IL-8. Elevated levels of salivary exosomal proteins (p=0.017), IL-6 (p=0.008), and IL-8 (p=0.0004), along with significant alterations in amino acid profiles, were observed in smokers compared with non-smokers. Additionally, protein (p=0.005) and IL-6 (p=0.004) levels were significantly elevated in oral cancer compared to non-smoker group. FTIR spectroscopy revealed distinct molecular fingerprints in exosomes, highlighting changes in protein and amino acid concentrations and indicating altered metabolism. This comparative cross-sectional study demonstrated that chronic smoking induces significant biochemical changes in salivary exosomes, establishing them as promising non-invasive biomarkers for early oral cancer detection. Elevated pro-inflammatory cytokines IL-6 and IL-8, along with altered amino acid profiles, may create pre-cancerous conditions. Notably, along with altered amino acid profiles, IL-6 levels progressively increase from smoking to oral cancer, highlighting its potential role in cancer progression.

Comparative genomic analysis unveiling the mutational landscape associated with premalignant lesions and early-stage gastric cardia cancer

Comparative genomic analysis unveiling the mutational landscape associated with premalignant lesions and early-stage gastric cardia cancer

Salivary proteomics and metaproteomics identifies distinct molecular and taxonomic signatures of type-2 diabetes

BackgroundSaliva is a protein-rich body fluid for noninvasive discovery of biomolecules, containing both human and microbial components, associated with various chronic diseases. Type-2 diabetes (T2D) imposes a significant health and socio-economic burden. Prior research on T2D salivary microbiome utilized methods such as metagenomics, metatranscriptomics, 16S rRNA sequencing, and low-throughput proteomics.ResultsWe conducted ultrafast, in-depth MS-based proteomic and metaproteomic profiling of saliva from 15 newly diagnosed T2D individuals and 15 age-/BMI-matched healthy controls (HC). Using state-of-the-art proteomics, over 4500 human and bacterial proteins were identified in a single 21-min run. Bioinformatic analysis revealed host signatures of altered immune-, lipid-, and glucose-metabolism regulatory systems, increased oxidative stress, and possible precancerous changes in T2D saliva. Abundance of peptides for bacterial genera such as Neisseria and Corynebacterium were altered showing biomarker potential, offering insights into disease pathophysiology and microbial applications for T2D management.ConclusionsThis study presents a comprehensive mapping of salivary proteins and microbial communities, serving as a foundational resource for enhancing understanding of T2D pathophysiology. The identified biomarkers hold promise for advancing diagnostics and therapeutic approaches in T2D and its associated long-term complicationBDMThTingLBLH7tsE5UbVQVideo

Role of ITGB2 protein structure and molecular mechanism in precancerous lesions of gastric cancer: Influencing the occurrence and development of cancer through the CXCL1-CXCR2 axis.

Gastric cancer is a prevalent gastrointestinal tumor. In the classical cascade of gastric cancer development, the gradual progression from non-atrophic gastritis, atrophic gastritis, intestinal metaplasia, to intraepithelial neoplasia eventually leads to early gastric cancer. We investigated the proteomic characteristics of chronic gastritis (CG), low-grade intraepithelial neoplasia (low-grade LGIN), and early gastric cancer (EGC). Additionally, we utilized transcriptomic databases to explore the expression patterns of ITGB2 across different stages of gastric tissue and its correlation with the prognosis of gastric cancer. The expression of ITGB2 was confirmed in cytological experiments, revealing that ITGB2 can influence the onset and progression of gastric cancer via the CXCL1-CXCR2 axis. This finding suggests that ITGB2 represents a novel biomarker for gastric cancer, making it a potential target for accurate diagnosis and treatment.

Sociodemographic, behavioral, and clinical risk factors associated with cervical dysplasia: A case-control study.

Cervical dysplasia is a precursor lesion of cervical cancer, one of the leading causes of morbidity and mortality in women, especially in developing countries. This study aimed to identify the risk factors associated with the development of cervical dysplasia in women treated at the Santa María del Socorro Hospital in Ica, Peru, between 2017 and 2019. An observational case-control study was conducted with 92 cases of women with confirmed high-grade intraepithelial lesion and 184 controls with consecutive negative results in Pap smears. Sociodemographic, behavioral, and clinical data were collected. Bivariate and multivariate logistic regression analyses were performed to identify factors associated with precancerous cervical lesions. The factors significantly associated with cervical dysplasia were age under 35 years (odds ratio: 1.2; 95% confidence interval: 0.1 to 0.7), having a partner (7.4; 2.3 to 23.5), body mass index ≥ 25 (12.9; 3.9 to 42.0), more than three sexual partners (71.4; 16.4 to 310.9), bacterial vaginosis (101.2; 12.2 to 838.2), grand multiparity (39.0; 7.1 to 225.4), rural origin (0.2; 0.1 to 0.8), use of injectables (0.2; 0.1 to 0.6), and intrauterine devide (0.04; 0.01 to 0.2). Identifying these risk factors is crucial for cervical cancer prevention. It is recommended to implement early detection programs targeted at women with risk factors, especially those under 35 years and with multiple sexual partners.

Exploring the mechanisms of Yang Wei Shu granule for the treatment of chronic atrophic gastritis using UPLC-QTOF-MS/MS, network pharmacology, and cell experimentation.

Chronic atrophic gastritis (CAG) is a global disease of the digestive system and is an important precancerous lesion in the development of gastric cancer. Yang Wei Shu granule (YWSG), which evolved from the formula 'Warm Stomach Soup' of the Jin and Yuan Dynasties in China, is frequently used as a classic herbal compound in the treatment of CAG. However, the active ingredients and mechanisms by which it works are not clear. To elucidate the chemical composition of YWSG and investigate the potential mechanisms of YWSG on CAG by composition analysis, network pharmacology and cellular experimental studies. The chemical and blood-entry constituents of YWSG were analyzed by ultra-high performance liquid chromatography-Quadrupole tandem time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). Subsequently, potential targets of YWSG for CAG treatment were identified through utilization of publicly available online resources. The YWSG-component-target-pathway network and protein-protein interaction (PPI) network were constructed using Cytoscape software. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of potential targets was performed using the DAVID database. Finally, a cellular model of lipopolysaccharide (LPS)-activated RAW 264.7 macrophages was established and validated by in vitro experiments. A total of 150 compounds in YWSG and 47 blood-entry constituents were identified by using UPLC-QTOF-MS/MS. Based on network pharmacology, a total of 132 target genes were identified as being involved in the therapeutic effect of YWSG on CAG. Network pharmacology and molecular docking results suggest that AKT1, PIK3CA, PTPN11, SRC and STAT3 may be potential targets of YWSG for the treatment of CAG. Cellular experiments showed that the YWSG-containing serum had no cytotoxic effect on RAW264.7 cells and could inhibit nitric oxide (NO) production and the expression of pro-inflammatory factors TNF-α, IL-6, and IL-1β. Additionally, it was observed to promote the expression of the anti-inflammatory factor IL-10 in LPS-stimulated RAW264.7 cells. The immunofluorescence results showed that YWSG treated CAG by inhibiting the PI3K-Akt pathway. The mechanism of action of YWSG on CAG was preliminarily elucidated using UPLC-Q-TOF-MS/MS, network pharmacology and in vitro experiments. The main active components and potential targets of YWSG were investigated, providing a scientific basis for further research.

Feasibility of cinobufacini for the treatment of oral premalignant lesions: an open-label pilot trial

Feasibility of cinobufacini for the treatment of oral premalignant lesions: an open-label pilot trial

Process Evaluation of Quality of Precancerous Cervical Lesion Screening Program in Selected Public Health Centers in Addis Ababa, Ethiopia.

Cervical cancer is the second most prevalent disease among Ethiopian women of reproductive age and a serious gynecological malignancy affecting women regionally. About, 3,235 deaths and 4,648 new cases are reported nationwide each year. Precancerous cervical screening programs face many difficulties in settings with limited resources, despite their severity, such as a lack of medical supplies and equipment, poorly trained healthcare workers, a heavy workload for current staff, low professional compliance, and insufficient support from medical facilities. Furthermore, the quality of screening services is not well-supported by data in many places, which makes efforts to enhance these programs even more difficult. Improving service quality and customer satisfaction requires an understanding of the accessibility of critical screening tools and the skill of healthcare providers. Hence, this study aims to evaluate the process quality of the pre-cancerous cervical lesion screening program at selected public health centers in Gullele sub-city, Addis Ababa, Ethiopia. A case study design involving both quantitative and qualitative methods was conducted from April 09 to May 10, 2022. The study was conducted based on clinical guidelines and previously published evidence in peer-reviewed journals. A total of nine (n = 9) public health centers were involved in the study. A total of 223 study participants for service program evaluation. For the qualitative study, 12 key informants were interviewed at exit consecutively. Additionally, resource inventory and record review were conducted. Data were analyzed using SPSS for Windows version 25. Multi-variate logistic regression was used to check the association between the outcome and independent variables. Multivariate logistic regression was analyzed when the p-value was less than or equal to 0.25 in bivariate binary logistic regression, considering the statistical significance at p-value < 0.05. Qualitative data were analyzed manually by summarizing into a key thematic area. The evaluation findings were interpreted based on a predetermined judgment matrix with stakeholders during the evaluability assessment. From quality perspectives, study found that, pre-cancerous cervical lesion screening service concerning program resource availability was measured to be 80%, which was good. In terms of satisfaction, the study found that 88% of clients were satisfied with the precancerous cervical lesion screening service provided by health centers. Occupational status of a government employee (AOR: 0.04; 95% CI: 0.003,0.63), educational status with no formal education (AOR: 0.04; 95%CI: 0.006, 0.23), long-term use of contraceptives (AOR: 3.70; 95%CI: 1.34, 10.21), and having multiple children up to three (AOR: 3.27; 95%CI: 1.3, 9.44) were significantly associated factors with client satisfaction on screening services for precancerous cervical. However, while the overall program implementation scored 78.67%, categorized as good, certain areas require improvement. Compliance with national guidelines among healthcare professionals were rated at 74%, indicating a need for enhanced adherence to established standards. Qualitative findings revealed that trained providers often handle multiple responsibilities, leading to service quality challenges due to overburdening. Additionally, financial constraints hinder the availability of essential equipment and medications, posing significant barriers to effective service delivery. In conclusion, although the level of satisfaction with service provision was good and the overall quality of service was acceptable. However, the availability of necessary resources and compliance of health care providers to national guidelines need improvement. We recommend more efforts be exerted on improving providers' compliance and availing of necessary resources to enhance the status of pre-cancerous cervical cancer screening services.

Modeling and the Use of Surrogate Endpoints: Is This a Valid Approach?

Development of novel colorectal cancer (CRC) screening tests is a dynamic field. Decision analytic modeling based on inputs derived from rigorous prospective studies informs CRC screening guidelines. Exploratory modeling may have a place in early phases of test development. We explored whether (1) surrogate endpoints for long-term, programmatic effectiveness, and cost-effectiveness could be potentially informative in early stages of test development and (2) whether rapid exploratory modeling with a web-based tool would be feasible. First, based on comparisons with published estimates for reductions in CRC mortality with various screening tests in four established decision analytic models of CRC screening, the surrogate endpoint of the number needed to colonoscope to detect one CRC or advanced precancerous lesion (APL) in round 1 of screening appears to hold promise as a measure of clinical effectiveness. Similarly, based on comparisons with published estimates for cost/quality-adjusted life-year gained with screening in the four models, the surrogate endpoint of cost to detect one CRC or APL in round 1 of screening appears to hold promise as a measure of cost-effectiveness. Second, exploration of the impact of lowering the screening initiation age in Israel from age 50 to 45 with the web-based EU-TOPIA tool, compared with the results of a recently published comprehensive modeling study, suggests that exploratory modeling of programmatic screening may be feasible with relatively low time demand vs. that required for typical full-length modeling publications. Further validation in other models and with a broader set of test performance characteristics is prudent before surrogate endpoints or rapid modeling are incorporated into the novel test development process.

Correlation between skin cancer and therapy with anti-IL monoclonal antibodies in patients affected by moderate-to-severe psoriasis: an observational monocentric study.

Our study aimed to investigate the correlation between skin cancer and anti-interleukin (IL) therapy in patients with moderate-to-severe psoriasis. This was an observational monocentric study in which we enrolled a total of 235 patients in which 127 patients were affected by moderate-to-severe psoriasis and treated with anti-IL monoclonal antibodies (mAbs) for at least 6 months, whereas 108 patients affected by mild psoriasis were treated with topical therapies. Afterward, we performed a dermatologic visit to all the subjects, collecting anamnestic information including risk factors for skin cancer. We examined the skin lesions on their entire body by polarized and nonpolarized dermoscopy. A total of 21 suspicious lesions in the first group and 17 in the second one were removed and histologically analyzed. Twelve (9.4%) cancerous or precancerous lesions were found in the first group: seven (5.5%) basal cell carcinoma (BCC) and five actinic keratosis. The mean time to cancer onset was identified as 22 months after the start of four therapy, with an SD of 18 months, suggesting an earlier onset with respect to the start of therapy in our population. On univariate analysis, age (P = 0.001) and age of psoriasis onset (0.009) were statistically significant. Nine of 17 were skin cancers in the second group. Our study provided real-life evidence of the percentage of patients with skin cancers during therapy with anti-IL mAbs, demonstrating a good safety profile of the investigated drugs.

Effectiveness of the Traditional Japanese Herbal Medicine, Yokuinin (Kampo), in the Treatment of Cervical Precancerous Lesions

Effectiveness of the Traditional Japanese Herbal Medicine, Yokuinin (Kampo), in the Treatment of Cervical Precancerous Lesions

Chronic viral mimicry induction following p53 loss promotes immune evasion.

Epigenetic therapies facilitate transcription of immunogenic repetitive elements that cull cancer cells through 'viral mimicry' responses. Paradoxically, cancer-initiating events also facilitate transcription of repetitive elements. Contributions of repetitive element transcription towards cancer initiation, and the mechanisms by which cancer cells evade lethal viral mimicry responses during tumor initiation remain poorly understood. In this report, we characterize premalignant lesions of the fallopian tube along with syngeneic epithelial ovarian cancer models to explore the earliest events of tumorigenesis following loss of the p53 tumor suppressor protein. We report that p53 loss permits transcription of immunogenic repetitive elements and chronic viral mimicry activation that increases cellular tolerance of cytosolic nucleic acids and diminishes cellular immunogenicity. This selection process can be partially attenuated pharmacologically. Altogether, these results reveal that viral mimicry conditioning following p53 loss promotes immune evasion and may represent a pharmacological target for early cancer interception.