Advanced melanoma remains a major clinical challenge due to resistance to immune checkpoint inhibitors (ICIs, e.g., anti PD-1). Astragalus Polysaccharide (APS) is a clinically approved immunomodulator for cancer treatment. However, its interaction with anti PD-1 remains largely unknown. This study aims to explore the efficacy and underlying mechanism of APS combined with anti PD-1 in melanoma.

For in vivo studies, the anti-tumor effect of APS combined with anti PD-1 was evaluated in a B16-OVA melanoma mouse model. For mechanism exploration, immunohistochemistry, flow cytometry, ELISA, PCR array, qRT-PCR, Western blotting and confocal microscopy were employed to detect tumor immune microenvironment changes and related signaling pathway activation.

Unexpectedly, APS significantly antagonized the anti-tumor efficacy of anti PD-1 in melanoma mice. APS reversed anti PD-1-induced infiltration of CD4⁺ T cells, CD8⁺ T cells and dendritic cells (DCs) in the tumor microenvironment, and impaired DC maturation and CD4⁺ T cell activation. Mechanistically, APS significantly inhibited JAK-STAT1 signaling, downregulated MHCII master regulator CIITA, and subsequently reduced MHCII expression. Meanwhile, APS markedly suppressed TLR signaling and attenuated NF-κB mediated inflammatory responses in B16-OVA melanoma cells and DCs.

APS antagonized anti PD-1 efficacy by inducing an immunosuppressive microenvironment via dual inhibition of JAK-STAT1/CIITA signaling and TLR/NF-κB signaling. This study suggests that the combination of natural polysaccharides and ICIs may warrant caution, although further studies are needed to validate these findings and determine their clinical relevance.

To delineate the clinical characteristics, diagnostic criteria, therapeutic strategies, and prognosis of myasthenia gravis (MG) with thymoma-associated CRMP5/CV2 antibody-positive paraneoplastic neurological syndrome (PNS), thereby enhancing clinical recognition of this rare overlapping autoimmune disorder.

We retrospectively analyzed the clinical data of a 53-year-old male patient presenting with peripheral nerve injury as the initial manifestation, who was subsequently diagnosed with MG, invasive thymoma, and CRMP5/CV2 antibody-positive PNS. A comprehensive review of the relevant international literature was also conducted.

The patient had a 2-year disease course, initially presenting with limb numbness and unsteady gait, and gradually developing dysarthria, dysphagia, diplopia, and myasthenic weakness with characteristic diurnal fluctuation (worsening in the evening and improving in the morning). According to the Myasthenia Gravis Foundation of America (MGFA) clinical classification, the patient was categorized as Class IIIb (moderate generalized MG with predominant oropharyngeal involvement) at baseline. Serological tests confirmed positive for acetylcholine receptor (AChR) antibody in serum, as well as CRMP5/CV2 antibody in both serum and cerebrospinal fluid (CSF). Electrophysiological examinations revealed multiple peripheral nerve damage and a significant decremental response to low-frequency repetitive nerve stimulation (RNS). Chest CT demonstrated an invasive thymoma in the anterior mediastinum. The patient underwent thoracoscopic thymectomy, followed by sequential treatment with glucocorticoids, intravenous immunoglobulin and cyclophosphamide, as well as symptomatic supportive care and anti-infective management. After treatment, the neurological symptoms were significantly improved, and the condition remained stable during follow-up.

MG with thymoma-associated CRMP5/CV2 antibody-positive PNS represents a rare clinical entity with atypical onset and is highly susceptible to misdiagnosis. Combined detection of paraneoplastic antibodies and chest imaging is critical for early diagnosis, and thymectomy combined with standardized immunotherapy can effectively improve the clinical symptoms and long-term prognosis of patients.

In developing countries like India mouth neoplasm like oral cancer shows significant and growing public health burden. It is diagnosed late due to lack in awareness which contribute to poor prognosis. Mobile health (mHealth) is effective in educating underserved rural population Health Education through Text messaging (WhatsApp) can improve knowledge at community level.

This protocol evaluates the effectiveness of daily WhatsApp-based mobile text messages in improving oral cancer knowledge compared to traditional PowerPoint presentations among adult dental outpatient patients.

A total of 144 eligible adults (aged 18-70 years) attending the dental OPD at CHC Bentkar will be randomized 1:1 into an intervention group (daily WhatsApp text messages) and a control group (weekly PowerPoint sessions). Oral cancer knowledge will be assessed using a validated structured questionnaire at baseline (T0), and six months (T1) post-intervention. Sample size was computed using G*Power software 3.1.9.7; Cohen's d = 0.5; α = 0.05; power = 80%) with 10% attrition allowance.

Evidence on comparative telemedicine-based approaches for oral cancer awareness in Indian primary care settings remains sparse. This trial will generate data on the scalability and durability of digital health education strategies for awareness and prevention of oral cancer, and may inform policy toward mobile-platform-delivered public health programme.

https://ctri.nic.in/Clinicaltrials/rmaindet.php?trialid=150355&EncHid=46498.40290&modid=1&compid=19, identifier CTRI/2026/05/111134.

Adenosine accumulation within the tumour microenvironment is a major barrier to effective cancer immunotherapy, driving potent immunosuppression through adenosine receptor signalling. While current clinical strategies primarily target the A_2A adenosine receptor, emerging evidence suggests that adenosine-mediated immune regulation, particularly in human myeloid cells such as macrophages, involves coordinated signalling through both A_2A and A_2B receptors. In this study, we define for the first time the adenosine receptor pathways responsible for the immunosuppressive effects of the adenosine analogue 5'-N-Ethylcarboxamidoadenosine (NECA) in human monocyte-derived macrophages and determine the downstream consequences for T cell function. NECA-conditioned macrophages acquired an immunosuppressive, M2-like phenotype, characterised by reduced production of pro-inflammatory cytokines (IL-12, IL-23, IL-6, TNFα) and increased expression of VEGF-A and IL-10. Functionally, these macrophages impaired T cell effector responses, markedly reducing Th1-type responses as indicated by ablation of IFNγ production. Importantly, reversal of macrophage polarisation and restoration of T cell function could be achieved by simultaneous blockade of both A_2A and A_2B receptors. These findings identify the potential of simultaneously inhibiting the A_2A and A_2B receptors as a novel key strategy for overcoming adenosine-driven immunosuppression and enhancing the efficacy of cancer immunotherapies targeting the tumour microenvironment.

Renal glomus tumor (GT) is a rare neoplasm originating from glomus cells within the kidney. The subtype designated as uncertain malignant potential (UMP) is particularly rare, with limited literature available. Its clinical presentation and imaging features closely resemble those of renal cell carcinoma (RCC), making accurate preoperative diagnosis difficult. This case report aims to describe the clinical, radiological, and pathological features of a renal GT of UMP and to summarize previously reported cases to improve recognition of this rare entity. We report a case involving a 36-year-old male who was incidentally found to have a cystic-solid mass (5.8 × 5.1 × 4.2 cm) in the lower pole of the right kidney during evaluation for tinnitus. Contrast-enhanced CT suggested a diagnosis of RCC, prompting laparoscopic partial nephrectomy. Postoperative pathology revealed focal mild cellular atypia and a Ki-67 proliferation index of approximately 10%. Immunohistochemistry showed positivity for SMA and Collagen IV, focal positivity for CD34, and negativity for CD10, HMB45, Melan-A, Desmin, CK, and CK7. Based on histomorphology and immunoprofile, a diagnosis of primary renal GT with UMP was established. The patient recovered well postoperatively without further treatment, and no local recurrence or distant metastasis was observed during an 8-month follow-up. We reviewed the existing literature to summarize the clinical characteristics and diagnostic considerations of UMP-type renal GT, aiming to enhance recognition of this rare entity.

Oncology drug development continues to have a high attrition rate despite major advances in therapeutic modalities such as antibody-drug conjugates, bispecific antibodies, cell therapies, and cancer vaccines. Critical development decisions are often made under substantial uncertainty, creating a need for quantitative approaches that integrate diverse sources of evidence. Quantitative medicine (QM) and model-informed drug development (MIDD) provide a framework to support decision-making throughout the oncology drug development lifecycle by leveraging pharmacology, disease biology, clinical data, biomarkers, and computational modeling. This review highlights three potential applications of QM that address drug development challenges. First, tumor growth inhibition-overall survival (TGI-OS) modeling links longitudinal tumor dynamics with survival outcomes, enabling earlier assessment of treatment benefit and supporting Phase III go/no-go decisions using Phase Ib/II data. Second, pan-molecule modeling across multiple antibody-drug conjugates that share a common linker-payload construct. This QM approach characterizes the class-specific exposure-toxicity relationships and informs dose optimization strategies, as illustrated by peripheral neuropathy risk modeling for vc-MMAE-containing agents. Third, population pharmacokinetic modeling and clinical trial simulation can facilitate intravenous-to-subcutaneous bridging by predicting pharmacokinetic non-inferiority, optimizing dose selection, and reducing development risk, as demonstrated for pertuzumab/trastuzumab and atezolizumab. Collectively, these examples demonstrate how QM can improve confidence in critical development decisions, optimize benefit-risk assessment, and enhance development efficiency. Continued integration of quantitative approaches, including emerging artificial intelligence and mechanistic modeling methodologies, has the potential to improve the probability of success and accelerate the delivery of effective oncology therapies to patients.

Mammary tumours are the most common neoplasm in female dogs. Canine mammary tumours (CMTs) are appropriate models for human studies.

The present study aimed to diagnose CMTs pathologically and compare different tumour types by immunohistochemistry (IHC).

Histological features of various tumours were recorded. Moreover, haematological, biochemical and immunohistochemical changes were evaluated in affected animals.

Among 130 mastectomized dogs in veterinary hospitals in Tehran, Iran, 74 dogs were affected by various types of mammary tumours. The highest frequency of malignant tumours was related to carcinoma types (38/74; 51.4%) and the highest frequency of benign tumours was related to fibroadenoma (6/74; 8.1%). In malignant tumours, anaemia and monocytosis were observed compared to benign tumours. Serum ALT and ALP levels were also significantly increased in malignant tumours (p < 0.05) compared to benign tumours. The IHC showed the profile of adenoma (ductal and intraductal papillary) ER⁺/PR^-/HER2^-, benign mixed tumour ER^-/PR^-/HER2^-, carcinoma (mucinous, anaplastic) ER^-/PR^-/HER2^- and metastatic mast cell tumour ER^-/PR⁺/HER2^-. The highest expression of αSMA was recorded in benign tumours and the highest expression of Ki67 was recorded in metastatic mast cell tumour, benign mixed tumour and adenoma (p < 0.05).

Together, although the dog is a good model for studying mammary tumours, the variability of results in CMTs requires further studies in this field. An interesting finding of this study was the triple-negative profile in the benign mixed tumour, which had previously been reported only for malignant mammary tumours. In addition, the significant positivity of Ki67 expression (34%-66%) in benign CMTs is noted for the first time.

Ropeginterferon alfa-2b is a new-generation interferon therapy for the treatment of myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET). This investigation was designed to characterize its population pharmacokinetics-pharmacodynamics (PopPK-PD) and delineate exposure-response (E-R) relationships in ET. A population PK model was constructed utilizing aggregated data from five clinical trials, encompassing a study population of Asian and Caucasian patients with ET and healthy volunteers. A sequential modeling strategy was employed to evaluate the PK-PD with respect to key hematologic markers including platelet and white blood cell counts. Hematologic changes were effectively modeled using sigmoidal indirect-response models. Individual exposure metrics were subsequently simulated by a target-mediated drug disposition model and then applied in E-R analyses for reductions in the allele burden of MPN driver mutations JAK2V617F and CALR, and safety outcomes. Simulations indicated no significant disparities between ethnicities in ropeginterferon alfa-2b exposure or the extent of hematologic response. A correlation was observed between drug exposure and a decrease in JAK2V617F allele burden at 6 and 12 months of treatment. Exposure-safety assessments identified a risk of exposure-related adverse events, including reversible anemia. Taken together, the data provided a solid PK-PD framework and insights into the E-R relationships for ropeginterferon alfa-2b in the treatment of ET.

Support vector machines (SVMs) have been widely applied to high-dimensional molecular and related biomedical data for cancer detection and other clinical classification tasks. The evidence spans diverse cancer types, specimens, platforms, objectives, and validation designs, limiting direct comparison.

We systematically reviewed studies evaluating SVM-based models using molecular omics or high-dimensional omics-adjacent data for cancer-related clinical applications. Article-level characteristics, SVM implementation, feature selection, validation, comparator models, and reported performance measures were extracted. Risk of bias was evaluated with the Prediction Model Risk Of Bias Assessment Tool (PROBAST). Because the studies did not estimate a common clinically interpretable quantity, no meta-analysis, pooled estimate, median performance comparison, or statistical subgroup comparison was performed. Findings were synthesized descriptively by data modality, clinical task, validation approach, comparative modeling, and methodological quality.

Seventy-five studies met the revised eligibility criteria. Sixty used molecular omics data; the other 15 used omics-adjacent inputs (10 spectroscopy-derived, two sensor derived, two mixed-data, and one imaging-derived). Cancer detection was the leading application. Internal validation alone was reported in 60 studies; eight combined internal and external validation, four relied on external validation only, two reported no validation, and one remained unclear. Seventy-two studies contributed 544 article-level SVM performance entries. In a separate PROBAST assessment, 72 studies were rated at high overall risk of bias and three at unclear risk.

SVM-based models have been studied across a broad range of cancer-related applications, but the evidence is heterogeneous, predominantly internally validated, and frequently at high risk of bias. A single summary performance estimate would be misleading. This review maps the evidence and identifies cancer-specific, modality-specific, and externally validated questions suitable for future focused studies.

Cyclin E1 (CCNE1), a pivotal member of the cyclin family, governs the G1/S phase transition of the cell cycle by binding to and activating cyclin-dependent kinase 2 (CDK2), thereby initiating DNA replication and driving S-phase entry. In a broad spectrum of human malignancies-including breast, ovarian, gastric, and non-small cell lung cancers-amplification or overexpression of CCNE1 disrupts the orderly regulation of cell cycle progression, leading to uncontrolled proliferation, impaired DNA damage repair, and genomic instability. These oncogenic consequences are intimately associated with increased tumor aggressiveness, poor patient prognosis, and diminished therapeutic efficacy. This review provides an integrated examination of CCNE1 biology, spanning its physiological regulation in the cell cycle, the molecular mechanisms by which its dysregulation drives tumorigenesis and drug resistance, the clinical implications of CCNE1 amplification as both a prognostic biomarker and a predictor of therapeutic response, and the emerging strategies to target CCNE1-driven vulnerabilities. By synthesizing findings across diverse cancer types and regulatory layers, we evaluate the translational potential of CCNE1 as a diagnostic marker and therapeutic target, and highlight key challenges and opportunities for future investigation.