Chimeric antigen receptor (CAR) represents a novel targeted therapy that uses genetic engineering to modify effector cells for precise tumor cell targeting. Chimeric antigen receptor-T (CAR-T) cell immunotherapy, which employs T cells as effectors, has demonstrated significant efficacy in treating hematologic malignancies. However, its efficacy against solid tumors remains inadequate and is accompanied by toxic side effects, including cytokine release syndrome, neurotoxicity and on-target/off-tumor effects. In contrast to T cells, natural killer (NK) cells exhibit a broader source range and can non-specifically lyse tumor cells. Moreover, it can also reduce toxicity and side effects to some extent. This review comprehensively examines recent research progress on CAR-NK therapy for solid tumors, encompassing both in vivo and in vitro studies, with a focus on CAR-NK cell design and production methods. Drawing upon laboratory and clinical evidence, this review summarizes the current challenges and side effects associated with CAR-NK technology.

Plasmid DNA vectors are emerging as a versatile antigen delivery platform for personalized cancer vaccines. Here, we report a comprehensive preclinical evaluation of a modular DNA cancer vaccine that targets antigen-presenting cells and encodes tumor-specific antigens (TSAs), including neoantigens and endogenous retroviral (ERV) antigens. To specifically direct the TSAs to APCs, the chemokine C-C motif ligand 19 (CCL19) was incorporated, enhancing the magnitude and persistence of antigen-specific CD4+ and CD8+ T-cell responses. This resulted in strong anti-tumor activity in multiple murine models. Delivery via clinically relevant DNA methods, including electroporation and needle-free injection systems, further improved immune responses compared to standard syringe/needle injection. Pharmacokinetic and toxicological analyses of the CCL19 component demonstrated rapid systemic clearance and an absence of adverse effects, supporting its suitability for clinical application. The platform exhibited a favorable safety profile across repeated administrations at clinically relevant and escalated dosing regimens, including in combination with immune checkpoint blockade. Furthermore, in vitro and in vivo evaluation of multiple antigens confirmed consistent protein expression and sustained immunogenicity, irrespective of antigenic composition, underscoring the platform's robustness and translational potential for individualized cancer vaccine strategies. These findings demonstrate that the CCL19-targeted DNA vaccine platform is both immunologically potent and holds strong potential in personalized cancer therapy.

To examine the safety of omitting routine histopathological examination by determining the prevalence of cervical pathology in women after cervical amputation as part of pelvic organ prolapse (POP) surgery without pre-existing indication for histology and the necessity of additional treatment.

A cross-sectional study was performed using data of women who underwent cervical amputation as part of POP without pre-existing indication for histopathological examination, obtained from Palga, the Dutch nationwide pathology databank, between January 1991 and January 2022.

The prevalences of the following histological diagnoses were determined: Cervical Intraepithelial Neoplasia (CIN I-III), adenocarcinomas in situ (AIS), cervical carcinomas, and other malignancies.

In total, 14.887 patients were included in this study, with a median age of 61.4 years (SD = 11.7). The prevalence of CIN II+ lesions was 6.9 [95%-CI 5.6, 8.3] per 1000 women, while one cervical carcinoma (6.7 [95%-CI -0.6, 19.9] per 100.000 women) was reported (stage IA1 microinvasive squamous cell carcinoma).

This study found a prevalence of 0.7% for CIN II+ incidental findings in women undergoing amputation of the cervix as part of POP surgery. No additional treatments were required after the final histopathological results. The decision to omit routine histopathological examination could potentially be safe, offering the prospect of reduced healthcare costs and environmental impact. Healthcare professionals should individually assess the risks and benefits of omitting and/or replacing routine histopathological examination.

Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer, and the prognosis is poor due to distant metastasis. Thus, there is an urgent need to discover novel therapeutic targets and strategies to overcome metastasis. A series of in vitro and in vivo phenotype experiments were performed to investigate the role of phosphodiesterase 1A (PDE1A) in NSCLC. The RNA binding protein immunoprecipitation (RIP) assay, messenger RNA (mRNA) stability assay, and LC-MS/MS were performed to investigate the molecular mechanisms of PDE1A in NSCLC progression. PDE1A has been shown to promote metastasis and epithelial-mesenchymal transition (EMT) progression of NSCLC. In addition, NSCLC cells overexpressing PDE1A promoted angiogenesis by regulating exosome release. IL-6/JAK/STAT3 signaling pathway was highly enriched in PDE1A-coexpressed genes, and PDE1A promoted NSCLC metastasis by activating the STAT3 pathway. GO enrichment analysis of PDE1A-interacting genes showed that PDE1A might interact with YTHDF2 and participate in m6A-containing RNA binding. The binding between PDE1A and YTHDF2 was verified, and PDE1A regulated the STAT3 pathway by interacting with YTHDF2. The mechanism of the YTHDF2/PDE1A complex in regulating the STAT3 pathway was predicted by overlapping YTHDF2-interacting RNAs and genes coexpressed with YTHDF2 and STAT3. The interactions between YTHDF2 and target mRNAs were predicted, and there were three predicted targets of YTHDF2 with high scores: NRF2, SOCS2, and MET. Indeed, PDE1A interacted with YTHDF2, destabilized SOCS2, and activated the STAT3 pathway. Mechanistic data uncover a novel PDE1A/YTHDF2/STAT3 axis driving NSCLC metastasis and suggest potential therapeutic strategies for metastatic disease.

Cancer immunotherapy is a cornerstone of precision medicine, yet its efficacy is often hampered by the immunosuppressive and heterogeneous microenvironment of solid tumors. Biomimetic nanodelivery systems have emerged as promising tools to enhance therapeutic outcomes while minimizing off-target effects. Among these, platelet (PLT)-based systems offer unique advantages, including prolonged circulation, immune evasion, and tumor-targeting capabilities. Of particular value is their ability to localize to sites of injury, which is a feature that nanocarriers cannot achieve. This review explores the multifaceted role of platelets in tumor development and metastasis, highlighting their bidirectional interactions with tumors. It further discusses the application of PLT-based nanotechnology in cancer immunotherapy, emphasizing recent advancements in immune regulation, targeted therapy, and clinical translation. We also address the challenges and considerations in developing PLT-based platforms, outlining future directions for their optimization in cancer treatment.

The biology of tumor spread to bone is poorly understood, not least in classic Hodgkin lymphoma (cHL). We used gene expression profiling and immunohistochemistry to characterize the nodal tumor microenvironment of cHL cases with and without skeletal involvement at diagnosis. Gene expression profiling of 66 pretreatment lymphoma samples revealed that lymph nodes from patients with skeletal cHL (s-cHL) exhibited a higher abundance of cells expressing macrophage markers, particularly M2-like markers, than nodal-only cHL (n-cHL). These markers included CD163, MRC1 (CD206), MARCO, and SIGLEC1. Additionally, there was a notable downregulation of genes encoding B-cell-associated markers such as MS4A1 (CD20), CD19, PAX5, and CD79A/B. We further evaluated the protein expression of macrophage markers (CD68, CD163, and CD206) and the B-cell marker CD20 in 193 pretreatment lymphoma samples using immunohistochemistry. Our analysis revealed significantly higher expression levels of all three macrophage markers in s-cHL samples compared to n-cHL samples (p < 0.001). Conversely, the expression level of CD20 was significantly lower in s-cHL compared with n-cHL (p < 0.001). All three macrophage markers correlated positively with Ann Arbor stage, indicating their potential involvement in the dissemination of cHL in general. Our findings suggest a potential role for tumor-associated macrophages in the dissemination of cHL to bone.

This study aims to identify and evaluate the treatment gaps in patients undergoing endocrine therapy for breast and prostate tumors, and to propose integrative solutions for unmet needs.

The article provides a narrative review of three significant side effects of endocrine therapy among breast and prostate cancer patients: vasomotor effects, joint pain and stiffness, and sexual disorders. It also offers treatment options for these effects from the field of complementary and integrative medicine.

The adverse consequences of endocrine treatments in breast and prostate cancer patients reduce treatment compliance and significantly impair the patients' quality of life. Evidence-based complementary and integrative medicine modalities, including nutritional counseling, dietary supplements, homeopathic remedies, touch therapies, acupuncture, and mind-body treatments, may improve the patients' quality of life and alleviate the burden of side effects.

There is a need to improve the management of side effects unique to endocrine therapy. Integrating supportive care with complementary and integrative medicine offers a viable option to enhance the quality of life for these patients.

Gynaecological tumours present a broad spectrum of histological subtypes due to the diverse anatomical and tissue origin of the reproductive organs. Rare tumours affect less than 6 per 100,000 individuals annually, posing significant challenges in diagnosis and management due to limited clinical awareness. Indeed, treatment protocols rely on options developed for more common histotypes, which may have limited efficacy on these rare tumours. In recent years, collaborative international efforts have started to address these gaps, improving standards of care. A comprehensive understanding of rare tumours' clinical and imaging features is necessary for radiologists in order to provide clinicians with useful information for treatment planning. In this review, we adopted an organ-based outline, describing rare tumours of the uterine corpus (leiomyosarcoma, endometrial stromal sarcoma, carcinosarcoma), cervix (gastric-type adenocarcinoma), and ovary (cystadenofibroma, lipid-poor teratoma, struma ovarii, immature teratoma, dysgerminoma). Additionally, tumours occurring at multiple sites, including lymphoma, neuroendocrine tumours, and aggressive angiomyxoma, are discussed. The objective is to help radiologists become familiar with these uncommon entities, ultimately increasing awareness on this topic.

The anti-GD2 antibody Naxitamab requires complicated pain management due to significant adverse effects (AEs). Herein, we report the safety and feasibility of a simplified administration protocol. Between November 2021 and July 2023, 102 Naxitamab infusions were administered at Shaare Zedek Hospital with ketamine as the only analgesic drug during Naxitamab infusion. Pain was controlled in all the cases. Other grade 3-4 AEs, occurred in 10/102 infusions (10%), and none of the patients stopped Naxitamab due to infusion-related AEs. Single-agent ketamine is safe and effective for Naxitamab-infusion-related pain. Thus, its use is feasible in multiple clinical settings. Significant infusion-related AEs after the completion of the 3rd treatment cycle are rare.

The incidence of thyroid cancer keeps rising globally,with the majority being papillary thyroid carcinoma (PTC),which has a favorable prognosis.However,some aggressive PTCs exhibit different clinical behaviors and higher mortality risks,with the growth rate surpassing that of well-differentiated PTC and undifferentiated cancers.Therefore,achieving precise diagnosis and treatment of thyroid carcinoma presents a significant challenge.Photoacoustic imaging is a molecular imaging technology that integrates optical imaging and ultrasound,providing imaging information on structure,function,and molecules.Moreover,it can utilize exogenous contrast agents to realize tumor treatment,such as photothermal therapy,serving as a promising technology for precise diagnosis and treatment of thyroid carcinoma.Researchers both domestically and internationally have explored the application of photoacoustic imaging in the precise diagnosis and treatment of thyroid tumors.This article reviews the research progress,elucidates the advantages and limitations of photoacoustic imaging in the diagnosis and treatment of thyroid carcinoma,and prospects on the precise diagnosis and treatment of this disease.