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Thymoma-associated anti-AMPAR encephalitis with myasthenia gravis: a case report.6 days agoThymoma can trigger a spectrum of paraneoplastic neurological disorders, including autoimmune encephalitis (AE) and myasthenia gravis (MG). However, the sequential development of anti-α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) autoimmune encephalitis followed by MG in the same patient is rarely reported.
To describe the clinical presentation, diagnostic work-up, treatment response, and outcome of a patient who developed thymoma-associated anti-AMPAR encephalitis and later presented with MG.
We retrospectively reviewed the medical records, imaging findings, laboratory results, and treatment course of a 49-year-old man who was evaluated at our institution. Serum and cerebrospinal fluid (CSF) autoantibodies were screened using cell-based assays and indirect immunofluorescence.
The patient initially presented with subacute cognitive decline, confusion, and behavioral changes. CSF analysis revealed mild lymphocytic pleocytosis. Anti-AMPAR antibodies were positive in both serum and CSF, and contrast-enhanced chest computed tomography (CT) scan showed an anterior mediastinal mass consistent with thymoma. High-dose intravenous methylprednisolone followed by tapering oral prednisone, plasma exchange (PE), and intravenous immunoglobulin (IVIG) and rituximab led to marked neurological improvement. Two months after discharge, he developed left-sided ptosis, diplopia, and dyspnea. Repetitive nerve stimulation showed a decremental response, and serology was positive for acetylcholine receptor (AChR), titin, and ryanodine receptor (RyR) antibodies, establishing the diagnosis of MG. Symptoms improved substantially with prednisone and tacrolimus, and subsequent thymectomy combined with efgartigimod further achieved sustained clinical remission.
This case illustrates that patients with anti-AMPAR encephalitis should be closely monitored for the subsequent emergence of MG, particularly when an underlying thymoma is present. Comprehensive antibody profiling is essential for early recognition and targeted immunotherapy. Long-term immunosuppression combined with tumor-directed treatment may be required to prevent relapses of both disorders and achieve optimal clinical outcomes.CancerCare/Management -
CALB2 mediates tumor progression and immune escape in colorectal cancer by shaping an inhibitory immune microenvironment.6 days agoColorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, characterized by a highly immunosuppressive tumor microenvironment (TME) that facilitates immune evasion and tumor progression.
Integrated analysis of TCGA and GEO datasets was performed to evaluate CALB2 expression and its prognostic significance in CRC. Functional experiments including proliferation, migration, colony formation, and apoptosis assays were conducted following CALB2 knockdown. Co-culture assays and multiplex immunohistochemistry (mIHC) were used to assess TME remodeling.
Elevated CALB2 expression correlated significantly with poor prognosis in CRC patients. CALB2 knockdown suppressed CRC cell proliferation, migration, and colony formation, while promoting apoptosis. CALB2 silencing also reprogrammed TME by inducing macrophage M1 polarization, enhancing CD8+T cell cytotoxicity, and reducing immunosuppressive cell infiltration. Mechanistically, CALB2 activated the STAT3 signaling pathway to promote CCL5 secretion, facilitating M2 polarization of macrophages and activation of fibroblasts.
Our findings identify CALB2 as a critical regulator of tumor progression and immune escape in CRC, acting through dual oncogenic and immunomodulatory mechanisms. CALB2 represents a promising therapeutic target for enhancing immunotherapy efficacy in CRC.CancerCare/ManagementPolicy -
Drug resistance mechanisms of immunotherapy and translational strategies for reversing resistance for hepatocellular carcinoma: from bench to bedside.6 days agoHepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and remains a major therapeutic challenge. In recent years, immune checkpoint inhibitors (ICIs), represented by PD-1/PD-L1 and CTLA-4 inhibitors, have revolutionized the field of HCC treatment and become the cornerstone of standard immunotherapy regimens, drastically altering the treatment landscape for advanced and unresectable HCC. However, primary and/or acquired drug resistance remains the leading cause of treatment failure, severely limiting the long-term clinical benefits of immunotherapy for HCC patients. This review aims to systematically summarize current research on immunotherapy for HCC, with a focus on drug resistance mechanisms across multiple dimensions: immunosuppressive tumor microenvironment, intrinsic tumor cell factors, and systemic and environmental influences. Potential strategies to overcome resistance are discussed, such as rational combination therapy with antiangiogenic or targeted agents, novel immune targets, nanotechnology-enabled precise delivery, and tumor organoid models for personalized treatment. Future advancements should focus on precision multimodal combinations, innovative therapeutic platforms, and individualized strategies guided by multi-omics and AI, aiming to overcome efficacy bottlenecks and improve patient survival.CancerCare/Management
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Role of innate immunity in the development of cancer immunotherapy immune-mediated adverse events.6 days agoImmune checkpoint inhibitors (ICIs) have transformed modern cancer therapy by restoring antitumor T-cell responses through blockade of immune tolerance pathways such as CTLA-4 and PD-1/PD-L1. However, the same immune activation that underlies their clinical efficacy can also lead to immune-related adverse events (irAEs), a broad spectrum of inflammatory and autoimmune toxicities that may affect virtually any organ system. The incidence and severity of these events vary according to the specific agent, tumor type, and treatment strategy. While irAEs have traditionally been attributed to dysregulated adaptive immunity, emerging evidence highlights a central and previously underappreciated role for innate immune mechanisms. In this review, we integrate the concepts of immunosurveillance and tumor immunoediting to illustrate how innate immunity contributes to both effective antitumor responses and immune-mediated toxicity. We describe how damage-associated signals and tumor microenvironment cues reprogram innate immune populations-including neutrophils, macrophages, dendritic cells, myeloid-derived suppressor cells, and innate lymphoid cells-toward pro-inflammatory or immunosuppressive states that influence therapeutic outcomes and toxicity risk. Finally, emerging biomarkers are highlighted and key knowledge gaps that currently limit the prediction and prevention of irAEs, positioning innate immunity as a critical regulatory axis and a promising target for developing strategies to mitigate toxicity without compromising anticancer efficacy.CancerCare/Management
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Histopathological spectrum of ocular masses in a tertiary eye center in Northern China: a 12-year retrospective analysis.6 days agoTo characterize the clinicopathological spectrum of ocular masses diagnosed over 12 years at a tertiary referral center in Northern China and identify demographic and regional patterns relevant to clinical practice.
We retrospectively reviewed 1,345 ocular masses diagnosed at Jinan Second People's Hospital between February 2014 and July 2025. Cases were identified from pathology archives and included patients with surgical excision or biopsy and definitive histopathology. Data on age, sex, anatomic location, and mass type were analyzed. Classification followed AFIP atlas standards and ICD-O coding.
Of the 1,345 masses, 1,146 (85.2%) were non-malignant and 199 (14.8%) malignant. Lesions were located in the eyelid (35.2%), ocular surface (35.7%), intraocular region (1.8%), and orbit (27.3%). For eyelid masses, nevi (20.8%) and cysts (11.2%) were the most common non-malignant lesions, and basal cell carcinoma (55.6%) and sebaceous gland carcinoma (24.2%) dominated malignancies. For ocular surface masses, the top non-malignant lesions included cysts (20.0%) and inflammatory lesions (18.1%), and malignant melanoma (34.6%) and squamous cell carcinoma (26.9%) were the leading malignancies. Most intraocular masses (20/24) were malignant, and the majority was melanoma (16/20). For orbital masses, hemangiomas (21.1%) were the most frequent benign lesions, and lymphoma (51.9%) was the leading malignancy. The majority of malignancies occurred in patients aged > 60 years (132/199, 66.3%). Compared to patients aged 18-60 years, those aged < 18 years had significantly lower odds of malignancy (OR = 0.21, 95% CI 0.08-0.59), whereas those > 60 years had significantly higher odds of malignancy (OR = 3.29, 95% CI 2.37-4.56).
Most ocular masses were non-malignant. The overall risk of malignancy increased significantly after age 60, and this trend was primarily driven by extraocular lesions.CancerCare/Management -
High prevalence of subclinical thyroid nodular disease in autopsies from Mexico with low frequency of NIFTP.6 days agoThe prevalence of thyroid nodular disease (TND) varies depending on study type. Nevertheless, a study including autopsies of patients from all over the country, covering almost three decades, is required to deepen our understanding of benign, borderline, and malignant lesions after the World Health Organization 2022 update. This study aimed to identify the prevalence of follicular TND (FTND), borderline, and malignant nodules in autopsies from a third-level hospital in Mexico City, as well as to determine the association between salt iodination and thyroid nodule genesis.
Autopsies performed between 1992 and 2019 were considered if archived thyroid remnants and clinical data were available. Cases with known premortem thyroid pathology were excluded. Nodules were considered diagnosed if gland morphology was grossly distorted.
The study included 487 autopsies, of which 276/59.2% were women. The mean age was 46.6 years. Of 487 glands, 266 (55%) had TND. Nodular glands had a higher weight than normal glands (17.8 vs. 16.1 g), with a 1.9:1 female-to-male ratio. No increase in the prevalence of nodules was observed after 2004 when salt iodination was regulated (0.40 vs. 0.39; p = 0.969). The median age of patients with FTND was 49 years for men and 51 years for women. Papillary thyroid carcinoma was observed in 44/9.4% glands, and the recently characterized non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)/an indeterminate lesion was only identified in seven (1.5%) cases.
TND was not associated with salt iodine regulation in Mexico, and prospective studies are needed to explain this finding in this country. Understanding the prevalence of subclinical FTND, NIFTP, and carcinomas is relevant and can contribute to reducing the rate of overdiagnosis in thyroid pathology.CancerCare/ManagementPolicy -
Complementary and alternative medicine use among elderly cancer patients: a cross-sectional study in South Korea.6 days agoThe use of complementary and alternative medicine (CAM) is common among elderly male cancer patients; however, evidence is limited on its prevalence, characteristics, and determinants in Korea. This study examined the prevalence, patterns, and reasons for CAM use, and identified factors associated with its use among elderly male cancer survivors.
A cross-sectional survey was conducted with 420 cancer patients aged ≥65 years attending outpatient clinics of the Veterans Hospital System, a 1,000-bed secondary hospital in Seoul, Korea. Data on CAM utilization, modalities, reasons for use, and information sources were collected using structured questionnaires. Multivariate logistic regression was used to identify demographic and clinical factors associated with CAM use.
Among participants, 60.0% reported using CAM. The most common modalities were exercise (brisk walking, 49.4%) and dietary interventions (42.9%). The primary reason for use was immune enhancement (61.6%), and family members or relatives were the main information source (42.1%). Multivariate analysis revealed that being married (OR 2.49, 95% CI 1.40-4.45), having prostate cancer (OR 2.14, 95% CI 1.36-3.35), and undergoing surgery (OR 1.62, 95% CI 1.07-2.45) were significantly associated with CAM use.
CAM use is highly prevalent among elderly male Korean cancer patients, particularly among married men, prostate cancer patients, and those who have undergone surgery. Oncologists should incorporate discussions about CAM into survivorship care, and further studies are warranted to assess the impact of CAM modalities on quality of life and clinical outcomes.CancerCare/Management -
CAR T cell engineering approaches to minimise toxicities.6 days agoFor the treatment of many forms of cancer, cell- and gene-based therapies are showing promise in both pre-clinical data and clinical trials. In particular, CAR T cell therapies, of which there are now 7 FDA-approved products, have shown ground-breaking results in haematological cancers such as multiple myeloma and B cell malignancies. Recent research is also attempting to develop effective CAR T cell therapies for solid tumours, with varying success. One of the key challenges faced by CAR T cell therapy is balancing strong cytotoxic activity for an effective treatment with preventing severe and potentially lethal toxicities, such as Cytokine Release Syndrome and Immune Effector Cell-Associated Neurotoxicity Syndrome. This mini review discusses some of the potential solutions that scientists have devised to overcome toxicities and improve existing CAR T cell therapies.CancerCare/Management
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From organelles to therapy: rethinking combined hepatocellular-cholangiocarcinoma.6 days agoCombined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary malignant hepatic neoplasm, defined by the concurrent presence of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) components, which vary in proportion and degree of differentiation. Characterized by insidious onset, high invasiveness, and marked heterogeneity, cHCC-CCA often eludes early diagnosis, leading to a generally dismal prognosis. Its survival outcomes typically fall between those of HCC and intrahepatic cholangiocarcinoma (iCCA). Epidemiological data derived from surgical resection specimens and percutaneous biopsy samples indicate that cHCC-CCA accounts for approximately 0.4%-14.2% of all primary liver cancers. Due to its rarity, standardized treatment protocols are currently lacking. Surgical resection and liver transplantation are considered the primary potential curative approaches. However, only a minority of patients meet surgical criteria at diagnosis, and postoperative recurrence rates are substantially high. For non-surgical candidates, local or systemic therapies are generally administered based on treatment regimens for HCC or iCCA. Additionally, the pronounced genetic and molecular heterogeneity of cHCC-CCA significantly compromises the efficacy of current therapeutic strategies. Its unique biological behaviors, histological features, and immunophenotypic profiles present multifaceted challenges to diagnosis, treatment, and research endeavors. This review aims to comprehensively synthesize the classification systems and pathological characteristics of cHCC-CCA, with a particular focus on the underlying organelle dysfunction. By integrating advances in clinical diagnosis and management, we seek to enhance disease awareness and provide a new reference for clinical practice.CancerCare/Management
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Salivary biomarkers in oral cancer diagnosis: advancing conventional treatment strategies.6 days agoOral squamous cell carcinoma (OSCC) is a major global health challenge, with most cases being diagnosed at advanced stages. Traditional diagnostic methods are often invasive and costly, and can delay diagnosis. Saliva has emerged as a promising non-invasive source of biomarkers for OSCC detection. This highlights the need for accessible, non-invasive, and sensitive biomarkers for OSCC detection. This review critically evaluates the current status and future potential of salivary biomarkers in OSCC, with an emphasis on their diagnostic efficacy, sensitivity, specificity, clinical validation, and advantages over traditional serum- and plasma-based markers. Saliva is a promising liquid for biopsy due to its non-invasive collection and molecular richness. We summarize evidence on diverse salivary biomarkers, including microRNAs (miRNAs), proteins, metabolites, circulating tumor cells (CTCs), and circulating tumor DNA (ctDNA), highlighting their dysregulation in OSCC and diagnostic utility. Particular emphasis is placed on CTCs, ctDNA, and miRNAs, which demonstrate stability in saliva and potential for early detection. We further discuss advances in next-generation sequencing, mass spectrometry, and artificial intelligence/machine learning that enable the development of biomarker panels with improved diagnostic accuracy over single markers. Despite challenges such as sample heterogeneity and the lack of standardized protocols, salivary biomarkers hold strong potential to transform OSCC care by enabling earlier detection, guiding personalized therapies, and supporting non-invasive disease monitoring. However, achieving methodological standardization, validating biomarkers across diverse cohorts, and integrating them into clinical workflows are imperative before their routine application in practice.CancerCare/Management