• Construction of nomograms for predicting overall survival and progression-free survival in patients with high-grade serous ovarian carcinoma: a retrospective study.
    1 week ago
    The aim of this study was to identify independent prognostic factors and develop predictive nomograms for overall survival (OS) and progression-free survival (PFS) in patients with high-grade serous ovarian carcinoma (HGSOC).

    Information on patients primarily diagnosed with HGSOC at the Affiliated Hospital of Qingdao University from June 2008 to June 2018 was extracted. Kaplan-Meier (K-M) analyses were used to generate survival curves. We employed univariate and multivariate Cox regression analyses to determine independent prognostic factors, and prognostic nomograms for OS and PFS were developed.

    A total of 573 patients were included in the final study. The age at diagnosis, first-visit interval, peripheral blood neutrophil-to-lymphocyte ratio, the immunohistochemical expressions of estrogen receptor and progesterone receptor, and Federation of Gynecology and Obstetrics (FIGO) stage were independent prognostic factors associated with OS and PFS. Additionally, the immunohistochemical expression of Wilms' tumor-1 (WT-1) and neoadjuvant chemotherapy were also related to the OS, whereas the serum carbohydrate antigen 125 (CA125) level, the immunohistochemical expression of CK7, omentum metastasis, and postoperative adjuvant chemotherapy were independent prognostic factors linked to PFS. The area under the time-dependent receiver operating characteristic curve values of the nomograms were higher than those of the FIGO staging system. The calibration curves and decision curve analysis demonstrated the clinical applicability of the nomograms.

    We developed two new risk stratifications based on the total points of the nomograms. This study could provide a foundation for the development of more accurate predictive models that can assist clinicians in creating individualized treatment plans and improving the prognosis of HGSOC.
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  • Comparative Diagnostic Performance of Flow Cytometry, Aspiration, and Biopsy with Immunohistochemistry in Plasma Cell Neoplasms.
    1 week ago
    Background: Plasma cell neoplasms (PCNs) are a heterogeneous group of hematologic malignancies that require accurate and timely diagnosis for effective management. Despite the availability of multiple diagnostic tools, challenges remain due to clinical and morphological variability. This study aimed to compare the diagnostic performance of three key modalities, including flow cytometry (FCM), bone marrow aspiration (BMA), and bone marrow biopsy with immunohistochemistry (BMB+IHC), in patients with plasma cell neoplasms. Materials and Methods: A cross-sectional study was conducted on 52 patients with confirmed PCNs. Diagnostic outcomes from FCM, BMA, and BMB+IHC were evaluated and compared. Sensitivity, specificity, predictive values, and inter-method agreement were calculated using SPSS version 27. Results: BMB+IHC achieved the highest diagnostic yield (100%), followed by BMA (55.8%), while FCM demonstrated the lowest diagnostic rate (32.7%). Flow cytometry showed excellent specificity and a positive predictive value of 100%, but limited sensitivity (32.7-58.6%), resulting in a high rate of false negatives. BMA frequently underestimated plasma cell burden due to sampling variability and hemodilution. Collectively, the integration of all three methods provided complementary diagnostic value, reducing the risk of misclassification. Conclusion: Bone marrow biopsy with immunohistochemistry remains the gold standard for diagnosing PCNs. However, combining it with aspiration and flow cytometry offers a more comprehensive diagnostic framework, improving accuracy, minimizing false negatives, and supporting optimal patient management.
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  • An Uncommon Site for a Common Tumor: Pleomorphic Adenoma of the Accessory Parotid Gland.
    1 week ago
    Tumors of the accessory parotid gland are rare and often misdiagnosed because of their anterior location and proximity to the facial nerve. We report a case of pleomorphic adenoma arising from the accessory parotid gland in a middle-aged man presenting with a mid-cheek swelling for 20 years. Magnetic resonance imaging demonstrated a well-circumscribed lesion along Stensen's duct. Complete surgical excision was achieved with preservation of facial nerve function. Awareness of this uncommon entity and appropriate surgical planning are essential to ensure optimal outcomes.
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  • Hematopoietic Stem Cell Tropism Mediated Targeting of Breast Cancer Stem Cells via Alteration of Tumor Immune-Microenvironment.
    1 week ago
    The ontogenic development of hematopoietic stem cells (HSCs) occurs across diverse niches, with HSCs migrating from the aorta-gonad-mesonephros (AGM) to the fetal liver and finally residing in the bone marrow after birth, where adult HSCs replenish the hematopoietic system. The HSC niche critically regulates tropism and proliferation via factors secreted by the microenvironment interaction. Here, we hypothesized that HSCs display tropism toward the aggressive cancer stem cell (CSC) niches of triple-negative breast cancer (TNBC) and MCF-7 cells breast cancer, which exhibit high relapse rates and are potential targets for cell therapy. Our results demonstrate HSC-specific tropism toward breast CSCs, leading to interactions that trigger HSC differentiation into CD4+ and CD8+ subpopulations within the cancer microenvironment. Proteomics of migrated HSCs toward TNBC-CSCs/MCF-7 cells revealed significant upregulation of IL-7, Notch, and other proteins involved in T cell activation and migration pathways. Metabolomics of HSC-conditioned medium (HSC-CM)-treated CSCs/MCF-7 cells further demonstrated that HSC-CM arrests TNBC-CSC growth and cell cycle progression by altering the mitochondrial bioenergetics. This study highlights the potential of leveraging both HSCs and HSC-derived factors for personalized therapies targeting CSCs in TNBC.
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  • Application of Metagenomic Next-Generation Sequencing in the Diagnosis of Pneumonia in Patients With Cancer.
    1 week ago
    With the development of new sequencing technologies, metagenomic next-generation sequencing (mNGS) has become a diagnostic tool for respiratory tract infections. Patients with cancer may develop pneumonia caused by infections or antitumor therapy. Therefore, pneumonia in patients with cancer is more complex than that in healthy individuals. Currently, few reports are available on the use of mNGS for diagnosing pneumonia in patients with cancer.

    In this retrospective study, 14 patients with cancer diagnosed with pneumonia in March 2023 were enrolled from the Emergency Department of the Chinese Academy of Medical Sciences Cancer Hospital. Sputum samples from the patients were examined using conventional tests and mNGS to identify pathogens. The mNGS and conventional test results were compared to assess the diagnostic yield in patients with cancer.

    The overall pathogen detection rate of mNGS was 64.29% (9/14), with corresponding diagnostic sensitivity, specificity, false-negative rate and false-positive rate of 90.00%, 25.00%, 10.00% and 75.00%, respectively. Among 13 paired sputum specimens, mNGS exhibited a numerically higher pathogen detection rate (61.54%, 8/13) than conventional diagnostic assays (38.46%, 5/13). McNemar's paired chi-square test demonstrated no statistically significant difference between the two detection methods (p = 0.37), and Kappa concordance analysis generated a coefficient of 0.27 (p = 0.23), suggesting poor inter-method consistency. Compared with conventional tests, mNGS detected additional pathogens in 8 specimens and identified a greater number of pathogens in 9/14 (64%) samples. Moreover, mNGS results led to diagnostic revisions and subsequent antimicrobial therapy adjustments in 64% (9/14) of enrolled patients. Additionally, mNGS detected antibiotic resistance genes in five patients, which provided guidance for antibiotic selection.

    Metagenomic next-generation sequencing (mNGS) showed potential value in pathogen detection, as it appeared to identify pathogens more rapidly and comprehensively than conventional methods. It may provide auxiliary support for the diagnosis and treatment of pneumonia in this vulnerable population.
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  • Cervical Cancer Screening Utilization Among Female Health Workers in Ethiopia: A Systematic Review and Meta-Analysis.
    1 week ago
    Despite the high incidence of cervical cancer, the screening coverage is low in developing countries, including Ethiopia. This study aimed to assess the pooled prevalence of cervical cancer screening and its determinants among female health workers in Ethiopia.

    All published literatures were searched using extensive international databases such as PubMed, Web of Science, Science Direct, Google Scholar, HINARI, Scopus, and Cochrane Library. The pooled prevalence of cervical cancer screening and the effect size of its determinants were illustrated using forest plots, and a DerSimonian-Laird random effect model with 95% Confidence Interval (CI).

    The pooled prevalence of cervical cancer screening among female health workers in Ethiopia was 17.4% (95% CI: 13.4, 21.3). Being trained in cervical cancer screening (AOR = 1.75, 95% CI: 1.05, 2.44), good knowledge about cervical cancer screening (AOR = 1.31, 95% CI: 1.02, 1.61), having multiple sexual partners (AOR = 2.06, 95% CI: 1.11, 301), and having a history of sexually transmitted infection (STI) (AOR = 2.96, 95% CI: 1.44, 4.47) were the main pooled predictors of cervical cancer screening utilization among female health workers in Ethiopia.

    Only one in every six female health workers was screened for cervical cancer in Ethiopia. Training in cervical cancer screening, knowledge of cervical cancer screening, multiple sexual partners, and STIs were the main determinants of cervical cancer screening utilization. Improving the health professionals' knowledge on cervical cancer screening through providing training on cervical cancer screening would be needed to increase the level of cervical cancer screening.
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  • Oncolytic viruses in brain cancer therapy: advances, challenges, and clinical trial outcomes.
    1 week ago
    Malignant intracranial tumors are a major cause of morbidity and mortality across age groups. To assess recent progress in glioblastoma (GBM) oncolytic virotherapy, literature was searched in PubMed and Google Scholar using the keywords glioblastoma, oncolytic virus, clinical trials, brain tumor, and oncolytic virotherapy resistance. Relevant studies published through 2024 were reviewed. Brain tumors vary in prevalence, but many have poor prognosis and low survival rates. Among available treatment approaches, oncolytic virotherapy has gained strong attention as a promising cancer therapy. Existing evidence shows that oncolytic viruses (OVs) can produce meaningful anti-tumor effects; however, tumor cells may resist OV activity through several mechanisms. These include alterations in tumor-cell molecular pathways, features of the tumor microenvironment, and physiological barriers within the patient's body. Some OVs have completed in vitro and in vivo studies and are now being evaluated in clinical trials, while others remain in early preclinical development. Clinical success depends on the intrinsic anti-tumor activity of OVs, methods used to enhance them, and their ability to incorporate new genetic and antigenic features. Such modifications may improve immune evasion, tumor targeting, tumor lysis, and anti-tumor immune responses, supporting development of next-generation OVs.
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  • The density of tumour infiltrating lymphocytes in oesophago-gastric cancer varies with disease stage, geographical region and treatment: a post hoc analysis of nine phase III clinical trials.
    1 week ago
    Tumour infiltrating lymphocytes (TILs) are a key component of the tumour microenvironment. To establish a clinically relevant TILs cut-off for patients with oesophago-gastric (OG) cancer, it is essential to know whether TILs density varies by patient and/or disease characteristics.

    TILs were quantified as TILs/mm2 (TILs density) by a deep-learning algorithm applied to digitised Haematoxylin/Eosin (H&E)-stained biopsies and resection specimens from 4628 patients from nine phase III trials. 4533 patients with TILs density and matched clinicopathological data were included in the final analyses. Associations between TILs density, disease stage, geographical region (UK versus Asia), sex, age, and treatment were analysed.

    Median TILs density was higher in pre-treatment biopsies from patients with early-stage versus late-stage disease (962 vs 479 TILs/mm2, p < 0.001). Within the same geographical region and disease stage, TILs density was similar across different chemotherapy regimens. In UK-led trials of early-stage disease, post-chemotherapy resections showed higher TILs density than chemotherapy-naïve resections (618 vs 571 TILs/mm2, p = 0.003). TILs density was higher in Asian tumours compared to UK tumours (1419 vs 571 TILs/mm2, p < 0.001). No significant associations were observed with age or sex.

    This is the largest study to date evaluating TILs density in OG cancer. TILs density varied with stage and geographical region but not by age or sex. These findings may explain enhanced response to immunotherapy observed in published studies of patients with early-stage disease and highlight the need to account for baseline TILs heterogeneity when interpreting TILs as a possible biomarker in future studies.
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  • MBD2 suppresses SFRP1 expression and promotes colorectal cancer development by blocking MED19 binding to its methylated promoter.
    1 week ago
    The Wnt signaling pathway antagonist SFRP1 is frequently silenced by promoter DNA hypermethylation in colorectal cancer (CRC). MBD2, a DNA methylation reader, is known to contribute to SFRP1 epigenetic silencing. Previous work showed that MBD2 critically suppresses SFRP1 expression without altering promoter methylation, though the underlying mechanism remained unclear. Elucidating how DNA methylation silences tumor suppressor genes, such as SFRP1, could reveal novel therapeutic targets with significant clinical potential.

    MBD2 was inhibited in CRC models using either siRNA or a small molecule inhibitor (KCC07). The effects on SFRP1 and β-catenin expression, Wnt pathway activity, cell proliferation, and apoptosis were assessed. Tumor growth was also evaluated in vivo. Mechanistic studies investigated the role of MBD2 in mediating MED19 binding to the SFRP1 promoter and its impact on RNA polymerase II CTD-S7 phosphorylation.

    The IC50 of KCC07 was 23.25 μM in SW480 cells, 26.83 μM in HCT116 cells, and 39.66 μM in NCM460 cells. Inhibition of MBD2, either genetically or pharmacologically with KCC07, upregulated SFRP1 expression, downregulated β-catenin, and suppressed the Wnt pathway. KCC07 treatment also inhibited CRC cell proliferation, promoted apoptosis, and suppressed tumor growth in vivo. Mechanistically, MBD2 was found to silence SFRP1 by blocking MED19 binding to its promoter, which subsequently reduced RNA polymerase II CTD-S7 phosphorylation and impaired transcription.

    This study reveals a novel mechanism whereby DNA methylation suppresses gene expression via MBD2, independent of changes in methylation status, by disrupting MED19 binding and subsequent transcription. Targeting MBD2 represents a promising therapeutic strategy for colorectal cancer.
    Cancer
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  • Population-Based First Estimates of the Effect of HPV Vaccination in Three Italian Areas Covered by Organised Cervical Screening.
    1 week ago
    In Italy, the first women invited for HPV vaccination at 15-16 years reached the age for cervical screening (25 years) in 2018. The real-world vaccination impact was evaluated. Women born in 1993-1996 invited for organised cervical screening in three Italian areas in 2018-2022 were eligible. After informed consent, they were tested for high-risk HPV and genotyped. Positives, triaged by cytology, were immediately referred to colposcopy if ASCUS+ (irrespective of genotyping); otherwise, recalled for cytology after 3 years. We estimated the relative (vaccinated with ≥ 2 doses vs. unvaccinated women) infection prevalence of three groups of genotypes: HPV16/18, HPV31/33/45 and HPV 35, 39, 51, 52, 56, 58, 59, 66, 68 ('non-vaccine preventable') and the relative positive predictive value (PPV) for histology-based CIN2+ detected at immediate colposcopy. Of 14,346 enrolled women, 34% had no vaccination, 66% ≥ 2 doses. The relative infection prevalence was 0.05 (0.03-0.10) for HPV16/18 without non-vaccine genotypes, 1.36 (1.23-1.50) for non-vaccine genotypes without HPV16/18 infections and 0.06 (0.03-0.12) for co-infections by both groups. The relative PPV for CIN2+ was very high (4.09; 1.40-12.01) in vaccinated women co-infected by HPV16/18 and non-vaccine types (4/9 vs. 7/84 cases) but reduced to zero in case of stand-alone HPV16/18 infections (0/12 vs. 15/117 cases). The CIN2+ relative detection in women infected only by non-vaccine types was 1.57 (0.87-2.82). The increase in infections and high-grade CIN from the pool of all non-vaccine genotypes requires further research (including pooling of data) to be confirmed with longer follow-up and on a larger study population.
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