• Beyond germ cell tumors: focus on Leydig cell neoplasms from a single-center experience.
    3 months ago
    Leydig cell tumors (LCTs) are rare testicular neoplasms that account for a small proportion of testicular tumors and are often diagnosed incidentally or on investigation of infertility or hormonal symptoms. Despite their generally benign behaviour, a small percentage may have malignant potential, which poses a diagnostic and therapeutic challenge due to the lack of standardizedguidelines.

    We retrospectively analysed four casesof histologically confirmed LCTs diagnosed and treated at a single institution between 2000 and 2024. Clinical, biochemical, radiologic, surgical, and pathologic data were collected and analysed.

    Patients presented with a variety of clinical histories, including testicular swelling, infertility, or incidental findings. Tumor size ranged from 1.8 to 3.5 cm. All patients underwent radical inguinal orchiectomy, and histology confirmed benign LCTs without high-risk features such as necrosis, mitotic activity, or vascular invasion. Hormonal profiles and imaging were key to the diagnostic process, although findings sometimes mimicked germ cell tumors. Adjuvant therapy was not required, and all patients remained disease-free at follow-up.

    This case series highlights the heterogeneity of LCT presentations and emphasizes the importance of accurate diagnosis, individualized treatment, and multidisciplinary management. Standardized protocols, greater awareness and timely imaging are essential to avoid overtreatment and improve outcomes in LCT patients.
    Cancer
    Care/Management
  • Heart failure in long-term survivors of childhood cancer - a systematic review and meta-analysis of population-based studies.
    3 months ago
    Heart failure is a well-recognised and serious non-malignant late complication among childhood cancer survivors. The primary aim of conducting this systematic review was to identify, critically appraise and synthesise population-based studies reporting on the incidence and/or prevalence of heart failure in 5-year survivors of childhood cancer (age < 18 years).

    We conducted this systematic review in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) in April 2021 (registration number: CRD42021247622) and published in June 2022. We searched databases Medline, Embase, Scopus, CINAHL, CAB International, AMED, Global Health, Psycinfo, Web of science and Google Scholar from their inception date until March 14, 2023. Screening, data extraction and quality assessment were conducted independently by two reviewers. The Effective Public Healthcare Practice Project tool was used for quality assessment.

    Following a comprehensive review of the 3,883 records, only four were found to be eligible for inclusion. The overall quality of the studies was evaluated as strong in two studies and moderate in the remaining two studies. A subsequent meta-analysis of three comparable studies yielded a cumulative incidence of 0.99% (95% confidence interval [CI] 0.57-1.42) over an extended period of 5.0-72.5 years (I-squared = 94.4%, p < 0.001).

    Existing population-based studies reporting on heart failure in 5-year childhood cancer survivors are few and heterogeneous. Future population-based studies comparing heart failure incidence in childhood cancer survivors with the general population would be of significant value.
    Cancer
    Cardiovascular diseases
    Care/Management
    Advocacy
  • Radiation-induced changes of reactive astrocyte distribution in mice as a late response to partial-brain proton irradiation.
    3 months ago
    After proton therapy of brain tumors, several studies have reported late image changes in follow-up magnetic resonance imaging, which result from blood-brain barrier (BBB) disruption. Astrocytes play a central role in the formation and maintenance of the BBB. To study the late response to partial-brain proton irradiation, preclinical mouse data were utilized to investigate the spatial distribution and dose dependence of reactive astrocytes.

    Previously, C57BL/6JRj mice were irradiated with protons targeting the right hippocampal region with single prescription doses of 45-85 Gy. After six months, mice were sacrificed and the excised brains axially cut into 3 µm thick slices and stained for glial fibrillary acidic protein (GFAP) to target astrocytes. Here, a workflow to segment the GFAP-positive area on slice images was established. The fraction of GFAP-positive area (GFAP+ fraction) was evaluated in the high-dose region in the right hemisphere and in the mirrored region in the left hemisphere. Dose distributions were simulated on pre-irradiation cone-beam computed tomography and co-registered to the histological slices.

    For all irradiated mice, the GFAP+ fraction in the right hemisphere was significantly increased compared to the left hemisphere and to a sham-irradiated mouse with a highly symmetric GFAP distribution. The GFAP+ fraction in the right hemisphere increased approximately linearly with prescription dose. For comparable doses, the cerebral cortex showed lower GFAP+ fractions than the midbrain.

    GFAP upregulation correlated with dose level and distribution. In combination with other markers and timepoints, these findings contribute to a comprehensive understanding of cellular response.
    Cancer
    Care/Management
    Advocacy
  • Enhanced ferroptosis by light-triggered biomimetic nano-erythrocyte membranes for tumor synergistic therapy.
    3 months ago
    Breast cancer is the most prevalent fatal cancer among women worldwide and the leading cause of death for women. Ferroptosis is a form of programmed cell death that relies on iron and is non-apoptotic, triggered by the inhibition of the cellular antioxidant system. Photodynamic therapy (PDT) employs photosensitizers to produce reactive oxygen species (ROS), increasing oxidative stress in tumor cells. When combined with ferroptosis, PDT can work synergistically to regulate intracellular redox balance. In this study, we designed engineered nano-erythrocyte membranes for targeted delivery of Chlorin e6 (Ce6) and cisplatin (DDP) to enhance breast cancer treatment. By using mild ultrasound, Ce6 and DDP were co-loaded onto the nano-erythrocyte membranes, combining ferroptosis inducers and photosensitizers to combat breast cancer. To improve targeting capability towards breast cancer, RGD cyclic peptides were modified onto the nano-erythrocyte membranes through a thiol-maleimide coupling reaction. The RGD-modified nano-erythrocyte membranes co-loaded with Ce6 and DDP not only inherited the good stability and significant biocompatibility of red blood cell membranes but also promoted the uptake by breast cancer cells, effectively inducing ferroptosis in these cells. In conclusion, this multifunctional 'natural' nanodrug delivery system provides an effective and safe method for PDT combined with ferroptosis for breast cancer treatment.
    Cancer
    Care/Management
  • Antineoplastic Effects of Thymoquinone on Pancreatic Atypical Acinar Cell Foci Treated With Azaserine.
    3 months ago
    The antineoplastic effects of thymoquinone (TQ) (which has antioxidant and anticarcinogenic effects) on neoplastic changes (atypical acinar cell foci, AACF) induced by azaserine were investigated, for the first time. Rats were randomly divided into five groups of 10 rats each (Cont, Tim, Az, AzTim1, and AzTim2). The Cont group was fed only with a standard diet. TQ (50 mg/L) was given orally (P.O.) to the Tim, AzTim1, and AzTim2 groups. TQ was given to Tim and AzTim1 after the first month, while AzTim2 group rats were given after the third month of azaserine injection, when AACFs began to form. Azaserine was injected intraperitoneally (i.p.) (30 mg/kg bw) to 2-weeks-old Wistar albino male rats in the Az, AzTim1, and AzTim2 groups. AACF load were observed to be statistically significantly higher in all categories in the Az group compared to the Cont group (p < 0.05). AACF load were statistically significantly lower in all TQ groups (AzTim1 and AzTim2) compared to the Az group and it was demonstrated with TQ-containing diet administration. This decrease indicates the antineoplastic effect of TQ on AACF and supports previous studies.
    Cancer
    Care/Management
  • Epigenetic Regulation and Targeted Therapy in Gall Bladder Cancer.
    3 months ago
    Gall bladder cancer is a formidable malignancy known for its aggressive nature and often late-stage diagnosis. In recent years, oncology has changed basic assumptions towards personalized and targeted therapies. Significant emphasis has been paid to research and clinical contexts about DNA methylation, histone changes, and microRNA alterations as key epigenetic pathways linked to the development of gall bladder cancer. The review delves into the potential of epigenetic markers as diagnostic and prognostic tools and discusses their utility in finding novel therapeutic targets. Targeted therapies have demonstrated effectiveness in addressing various types of cancer, and gall bladder cancer is no exception. The recent advancements in targeted therapies tailored for gall bladder cancer have been elaborated, underscoring the vital role of precision medicine in customizing treatment plans to suit individual patients. The review also examines the challenges and opportunities associated with the development of therapies specifically designed to target epigenetic changes, potentially offering treatment options that are both more efficacious and less toxic.
    Cancer
    Care/Management
    Policy
  • Cordycepin Inhibits Proliferation, Migration, and Promotes Apoptosis in Fibrosarcoma HT1080 Cells by Targeting Akt1 and Kinase Activity Through Network Pharmacology Analysis.
    3 months ago
    Fibrosarcoma cells exhibit low sensitivity to chemotherapy and significant drug resistance, emphasizing the urgent need for effective, low-toxicity therapeutic agents with reliable production methods and novel treatment strategies. Cordycepin (3'-deoxyadenosine) has shown promising therapeutic potential in cancer treatment. In this study, cordycepin was produced using a genetically engineered Pichia pastoris strain cultured in an inorganic salt medium and purified to over 98% purity via macroporous resin chromatography, providing a cost-effective production alternative. The effects of cordycepin on the human fibrosarcoma cell line HT1080 were assessed using microscopic examination, scratch assays, CCK-8 assays, and flow cytometry (Annexin V-FITC/PI staining). The results demonstrated that cordycepin significantly inhibited cell activity at an effective concentration of 100 μmol/L. Key observations included changes in cell morphology, reduced migration, inhibited proliferation, cell cycle arrest at the G0/G1 and G2/M phases, and induction of apoptosis. Network pharmacology analysis identified 31 potential targets of cordycepin in fibrosarcoma, with its effects on Akt1 (protein kinase B) and disruption of protein phosphorylation pathways emerging as key mechanisms underlying its therapeutic efficacy. Western blot analysis further confirmed that cordycepin simultaneously downregulated both the expression and phosphorylation levels of Akt in a dose-dependent manner.
    Cancer
    Care/Management
  • Immune Landscape and Prognostic Significance of Gene Expression Profiles in Bladder Cancer: Insights from Immune Cell Infiltration and Risk Modeling.
    3 months ago
    To explore the immunological underpinnings and prognostic potential of gene expression profiles in bladder cancer through comprehensive analyses of The Cancer Genome Atlas (TCGA) data. We used the TCGA data to identify differentially expressed genes (DEGs) and performed enrichment analysis to reveal the related biological pathways. Meanwhile, the least absolute shrinkage and selection operator (LASSO) algorithm was adopted to develop a prognostic model. Then we evaluated the performance of the model in both TCGA and GSE13507 datasets. Furthermore, we conducted a comprehensive investigation on the feature genes utilized in model construction, encompassing both gene expression profiling and survival analysis. Finally, immune infiltration analysis and drug sensitivity analysis were applied to elucidate the immunological basis of the disease and provide potential therapeutic strategies. We identified a total of 837 DEGs, with a focus on immune-related genes. Using the LASSO algorithm, we developed a prognostic model incorporating seven key genes-NXPH4, FAM110B, GPC2, STXBP6, CYP27B1, GARNL3, and PTGER3-which demonstrated strong predictive accuracy in both TCGA and GSE13507 datasets. Moreover, immune infiltration analysis revealed a higher abundance of M0 and M2 macrophages in high-risk patients, suggesting that macrophage polarization could be a potential therapeutic target to modulate the immune microenvironment. Drug sensitivity analysis further suggested that high-risk patients exhibit differential responses to several chemotherapy agents, with potential therapeutic implications. This study constructed an effective prognostic model, providing new insights and potential therapeutic targets for the personalized treatment of bladder cancer, which needs further validation.
    Cancer
    Care/Management
    Policy
  • Dentinogenic ghost cell tumor in a pediatric patient: A case report and literature review.
    3 months ago
    Dentinogenic ghost cell tumors (DGCTs) are rare odontogenic neoplasms constituting the solid variant of calcifying odontogenic cysts. Predominantly observed in adults, DGCTs are exceptionally rare in pediatric patients. This case report aims to contribute to the limited literature by presenting the clinical, radiographic, and histopathological findings of a pediatric patient with a DGCT and emphasizing the importance of early diagnosis.

    A 14-year-old male presented with facial asymmetry in the left mandible.

    Diagnostic imaging revealed a multilocular radiolucent lesion with impacted teeth, cortical expansion, and root resorption. Histopathological evaluation confirmed the DGCT diagnosis.

    The lesion was treated conservatively with enucleation and curettage, followed by a 3-year follow-up.

    Regular follow-ups demonstrated progressive bone regeneration with no evidence of recurrence. No postoperative complications were observed.

    Because of their high recurrence rate and potential for transformation into dentinogenic ghost cell carcinoma, early diagnosis and long-term follow-up are crucial for effective management in DGCT cases.
    Cancer
    Care/Management
  • Atypical presentation of secondary hepatic lymphoma with severe hepatic involvement: A case report and literature review.
    3 months ago
    While secondary hepatic lymphoma can develop in up to 50% of patients with non-Hodgkin lymphoma and approximately 20% of those with Hodgkin disease, it is uncommon for patients to present with severe hepatic involvement, manifesting initially as jaundice and abdominal pain. These nonspecific symptoms can complicate diagnosis and subsequently delay the initiation of appropriate treatment.

    A 68-year-old female presented to our hospital with complaints of abdominal pain and jaundice.

    Laboratory tests and clinical symptoms are often nonspecific for this atypical presentation of secondary hepatic lymphoma, and imaging findings can be challenging to distinguish. Histopathological examination remains the gold standard for diagnosis.

    Due to severe thrombocytopenia and coagulopathy, only low-dose prephase chemotherapy was administered along with supportive treatments, including platelet transfusion and coagulation factor supplementation.

    The patient was dead. No autopsy was performed, as the patient's family declined consent.

    Clinicians should maintain high vigilance for atypical presentations of lymphoma, especially when encountering unexplained cholestatic hepatitis and cytopenias, and promptly initiate diagnostic evaluations to avoid delays in treatment. A definitive diagnosis primarily relies on histopathological examination, with chemotherapy remaining the cornerstone of treatment.
    Cancer
    Care/Management
    Advocacy