Infectious Agents and Cancer最新文献

The complex interplay between parasites and cancer is yielding promising advances in the field of cancer therapeutics. This study explored the in vitro anti-cancer potential of parasite immunomodulators (antigens and antibodies) of Schistosoma mansoni, Trichinella spiralis, and Toxoplasma gondii on human HT-29 colorectal and HepG2 hepatocellular carcinoma cells using the MTT assay. Results revealed that those parasites' immunomodulators exhibited antineoplastic activity and demonstrated a statistically significant inhibition of both cancer cell lines' proliferation (P ˂0.05). Notably, Trichinella spiralis antigens and antibodies and anti-Toxoplasma gondii antibodies demonstrated the most statistically significant inhibitory effects on HT-29 colorectal cancer cells (36.65%, 49.9% and 50.43% respectively). For HepG2 hepatocellular carcinoma cells, Trichinella spiralis antigens and antibodies, as well as Toxoplasma gondii antigen, displayed the most statistically significant inhibitory effects (38.27%, 48.25% and 34.68% respectively). Interestingly, parasitic antibodies are particularly noteworthy, exhibiting the most significant inhibitory effects on both cancer cell lines. To the best of our knowledge, this is the first study to demonstrate the antineoplastic activity of parasites' antibodies against human colorectal cancer and hepatocellular carcinoma. These findings could enlighten the path for promising cancer therapeutic candidates. Future research should explore the antineoplastic potential of a broader range of parasites' immunomodulators and identify their mechanisms of action. This could represent a qualitative shift towards the development of innovative cancer therapeutic antibodies and cancer vaccine candidates of parasitic origin for cancer-targeted immunotherapy.

Burkitt lymphoma (BL) is a highly aggressive B-cell lymphoma with its occurrence and progression closely associated with Epstein-Barr virus (EBV) status. However, the molecular differences between EBV-positive and EBV-negative BL have not been comprehensively evaluated. Through targeted sequencing of a 475-gene panel in 27 BL cases, and RNA-seq and LncRNA-seq analyses of 25 cases, we found that EBV-negative tumors displayed a higher frequency of chromosomal amplifications, particularly at 7p12.2, 6q25.3 and 7q22.1. Two novel variants of KMT2D were identified in adult patients in the EBV-negative group. Furthermore, EBV-positive BL exhibited enriched FOXO1 mutations, in contrast to CCND3 hotspot variants in EBV-negative cases. Transcriptome profiling revealed 1,612 differentially expressed genes (DEGs), predominantly involved in the PI3K-AKT, Hippo, WNT, and mTOR pathways. LncRNA profiling identified three EBV-associated lncRNAs ((MSTRG.103766.1, MSTRG.33752.11, ENSTO0000400385.2) with potential prognostic relevance in BL. Immune deconvolution (CIBERSORT/xCELL) demonstrated elevated M1 macrophages infiltration in EBV-positive BL, which correlated with improved 24-month overall survival (68% vs. 41%, p = 0.02). SULT1C2P1 and KCNK5 emerged as M1-associated prognostic biomarkers. Our findings establish EBV as a key modulator of BL genomic instability and immune remodeling, leading us to hypothesize that EBV status defines distinct BL subtypes with unique therapeutic vulnerabilities, thereby enabling the future development of EBV-stratified precision therapies.

Background: Bladder cancer remains a global health challenge with marked demographic and regional disparities. Understanding long-term trends, risk factors, and projections is essential for effective prevention.

Methods: Data on bladder cancer were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021. We focused on the effects of age, sex, risk factors, and the socio-demographic index (SDI) on the burden of bladder cancer and calculated the average annual percent change (AAPC) via joinpoint regression. Mendelian randomization (MR) to assess causal risk factors, and Bayesian age-period-cohort (BAPC) models to forecast future burden.

Results: From 1990 to 2021, the global age-standardized incidence rate slightly declined (AAPC = - 0.269), prevalence increased (AAPC = 0.145), and both mortality (AAPC = - 0.840) and DALYs (AAPC = - 1.022) decreased significantly. The burden was significantly higher among males and older adults and showed substantial variation across SDI regions. Smoking and high fasting plasma glucose were strongly associated with bladder cancer DALYs, accounting for 27.8% and 7.4%, respectively. MR studies have confirmed that smoking and testosterone levels can increase the risk of bladder cancer. The prediction results indicate that the global age-standardized incidence rate will moderately decrease from 2022 to 2050.

Conclusion: Despite a gradual decline in mortality and incidence, bladder cancer continues to impose a substantial health burden, particularly among males and in high-SDI regions. Smoking and high fasting glucose are key modifiable risk factors. Sustained prevention and resource allocation are essential to mitigate the rising absolute burden in aging populations.

Background: Women Living with HIV (WLHIV) are at increased risk of persistent high-risk Human Papillomavirus (HR-HPV) infections and cervical cancer. However, data on HPV genotype distribution and cervical cytologic abnormalities remain limited in North Africa, particularly among women receiving effective antiretroviral therapy (ART).

Objective: To assess the frequency of cytologic abnormalities in WLHIV in Sétif, Algeria, identify HR-HPV genotypes, and evaluate associated immunovirological factors.

Methods: A cross-sectional study was conducted from January to December 2024 at the HIV/STI/AIDS Reference Center in Sétif. WLHIV aged ≥ 18 years who provided informed consent were included. Each participant underwent a gynecological examination, cervical cytology (Pap smear), HR-HPV genotyping by molecular biology, and immunovirological assessment (CD4 T-cell count, HIV viral load). Colposcopy and biopsy were performed when indicated.

Results: Among 115 enrolled participants, 100 smears were interpretable. Cytologic abnormalities : Atypical Squamous Cells of Undetermined Significance (ASC-US), Low-Grade/High-Grade Squamous Intraepithelial Lesions LSIL, HSIL) were found in 28% of WLHIV. HR-HPV infection was detected in 32% of participants, mainly genotypes HPV52, HPV16, and HPV18. A significant association was observed between HR-HPV positivity and high-grade lesions (HSIL) (p = 0.018; OR = 9.57, 95% CI: 1.02-89.48).

Conclusion: WLHIV in Algeria show a high prevalence of HPV-related cytologic abnormalities, even with adequate immune status and viral suppression. These findings emphasize the importance of regular cervical screening and support current global recommendations for comprehensive prevention strategies, including HPV testing and vaccination.

Background: In cervical screening, human papillomavirus (HPV)-positive women at 1-year retesting are typically referred to colposcopy. This study, by the use of extended genotyping, estimates the impact of distinguishing persistent from new infections in an effort to reduce colposcopy referral. It also evaluates whether the new infection rate varies according to genotyping, cytology, p16/ki67, and E6/E7 mRNA results.

Methods: We analyzed data from HPV-DNA-positive women at baseline in the NTCC2 trial genotyped with the Onclarity HPV assay. Eligible participants were Onclarity-positive women without baseline CIN2+ who had a cervicovaginal sample collected at least 10 months after baseline. Persistent infections were defined as cases with at least one common genotype between baseline and follow-up specimens. New infections were defined as cases positive for different genotypes at follow-up, with no baseline genotypes detected.

Results: Among 1,540 women included, 613 were Onclarity-positive at both baseline and 1-year retesting: 488 (79.6%) had persistent infections, while 68 (11.1%) had new ones. All the 11 CIN3 cases identified at follow-up occurred in women with persistent infections. The new infection rate was significantly higher in women with baseline single-channel compared to multiple channels positivity (13.3% vs 5.5%, p=0.001). Stratifying by age, persistence and new infection rates were significantly different among different age groups (respectively p=0.005 and p=0.009). No significant difference in both new infections and persistence rate was observed between baseline cytology positive and negative cases. Stratifying by baseline p16/ki67 results, we found a significantly higher rate of persistent cases among p16/ki67 positive cases and of new infections among p16/ki67 negative cases (respectively p=0.013 and p=0.016). E6/E7 mRNA findings affected only persistence rate showing a significant difference in the proportion of persistent cases between positive and negative cases (p=0.004), but did not affect new infection rate.

Conclusion: Extended genotyping classified 11.5% of 1-year HPV-positive cases as new infections. As 1-year HPV positivity accounts for about 60% of first-level colposcopies, this corresponds to about 7% of colposcopies. Baseline single-channel positivity, age, and p16/ki67-negative results may influence this proportion.

Trial registration: Clinicaltrials.gov registration number: NCT01837693, New Technology in Cervical Cancer 2 (NTCC2) study.