Lymphangiomas are uncommon congenital benign tumors of the lymphatic system. They are typically diagnosed at birth and develop during the first years of life. The tongue is the most commonly affected structure in the oral cavity. Lymphangioma circumscriptum of the tongue is a common cause of macroglossia in children, and this macroglossia can lead to complications such as exclusive nasal breathing, airway obstructions, impaired oral feeding, esthetic disfigurement, and difficulties in mastication, swallowing, and speech. This report discusses the successful treatment of lymphangioma circumscriptum of the tongue with sirolimus, an immunosuppressant drug. The extent of the lesion made traditional surgical management impossible without excessive morbidity, so the patient was managed medically. This case report was unique due to its entirely nonsurgical treatment approach. The patient completed a 17-month course of sirolimus monotherapy with response to treatment monitored using T2 MRI. There was excellent response to treatment, full resolution of symptoms, and no treatment-related toxicity.

Obesity is a major risk factor for colorectal cancer (CRC), yet the mechanisms linking obesity-associated gut dysbiosis to tumor progression remain unclear. Here, we show that a high-fat diet and fecal microbiota from patients with obesity-associated CRC deplete the GABA-producing commensal Bacteroides ovatus, resulting in reduced luminal GABA and accelerated tumorigenesis. Microbial GABA activates epithelial GABAB receptor signaling and induces TPI1 through the PI3K-HIF1α pathway. Increased TPI1-derived glyceraldehyde-3-phosphate inhibits PPP1CA, maintains YAP phosphorylation, restricts nuclear YAP activity, and suppresses pentose phosphate pathway flux, thereby limiting tumor growth. Consistently, obesity-associated CRC exhibits reduced fecal GABA, decreased TPI1 expression, and metabolic rewiring. A GABA-deficient B. ovatus mutant fails to restore GABA or suppress tumors despite normal colonization, whereas oral GABA supplementation or recolonization with wild-type B. ovatus markedly reduces tumor burden. These findings identify a microbiota-neurotransmitter-metabolism axis linking obesity to CRC and suggest microbiota-based GABA restoration as a potential preventive strategy.

Although macrophages are a powerful cell-based platform for cancer immunotherapy, their antitumor functions, such as phagocytosis and inflammatory responses, are limited by the immunosuppressive tumor microenvironment. Here, we show that decorating cancer cell membranes with bacteria-derived pathogen-associated molecular patterns (PAMPs) initiates phagocytosis and inflammatory responses of macrophages toward cancer cells involving various pattern-recognition receptor signaling pathways. Bacteria-derived PAMPs were formulated into membrane-decorating nanoparticles, and these nanoparticles reprogrammed immunosuppressive macrophages into inflammatory phenotypes. Cancer cell membrane-attached PAMP nanoparticles maintained their immunostimulatory responses, stimulating macrophages' antitumor functions. The fraction of phagocytic macrophages significantly increased when coincubated with membrane-decorated cancer cells, along with an increased secretion of inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Transcriptomic gene ontology analysis revealed that the response of macrophages to PAMP-decorated cancer cells resembled their response to bacteria, involving signaling pathways including inflammatory response and innate immune response. In a mouse model, locally injected membrane-decorating PAMP nanoparticles suppressed tumor growth. The therapeutic effect was more pronounced in combination with the chemotherapeutic drug doxorubicin. Median survival days significantly increased in both the PAMP nanoparticle and the PAMP nanoparticle plus doxorubicin combination group with complete remission cases, compared to the doxorubicin group. Our findings provide insights into the use of macrophages as a cancer immunotherapy modality.

Conventional type 1 dendritic cells (cDC1s) play a pivotal role in initiating CD8⁺ T-cell-mediated antitumor immunity, and their intratumoral abundance strongly correlates with immunotherapy efficacy. Here, we demonstrate that orally administered chenodeoxycholic acid (CDCA), a clinically approved metabolic modulator, accumulates in the tumor interstitial fluid (TIF) of tumor-bearing mice as its metabolite taurochenodeoxycholic acid (TCDCA), thereby potentiating the antitumor functions of cDC1s and CD8⁺ T cells through a gut microbiota-independent mechanism. Mechanistic studies revealed that CDCA mediates this immunomodulatory effect via TGR5 signaling, which enhances cDC1 functionality and subsequently promotes the proliferation and activation of tumor-specific CD8⁺ T cells. Clinical correlation analysis of human tumor specimens revealed a positive association between Takeda G protein-coupled receptor 5 (TGR5) expression and HLA-A/B/C/E/F/H levels, with elevated TGR5 expression significantly predicting improved overall patient survival. Moreover, CDCA exhibits synergistic antitumor effects when combined with anti-PD-1 immunotherapy and a poly I:C adjuvant, leading to robust tumor growth suppression and enhanced antitumor-immune responses. Overall, our study elucidates a novel immunoregulatory mechanism through which CDCA modulates tumor progression, highlighting CDCA and its bile acid derivatives as promising therapeutic candidates for cancer immunotherapy, providing a potential strategy to overcome resistance in cold tumors by revitalizing the cDC1-CD8⁺ T-cell axis.

Immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 inhibitors, have revolutionized the treatment of extensive-stage small-cell lung cancer (ES-SCLC). Chemotherapy combined with PD-1 or PD-L1 inhibitors has become the standard first-line treatment for ES-SCLC. However, with the broad application of immunotherapy, adverse events associated with this therapy have been increasingly reported by clinicians. The identification of atypical and specific manifestations of immune-related adverse events (irAEs) requires accumulated experience on the part of clinicians. In this article, we report the case of a patient over 50 years of age who was initially diagnosed with ES-SCLC. Clinical symptoms mainly manifested as allodynia of the abdominal wall following PD-L1 inhibition immunotherapy. This symptom progressed with continued immunotherapy and resolved after cessation of immunization and treatment with prednisone. A peripheral neuropathy antibody test revealed anti-GM4 IgG antibody positivity. On the basis of the patient's clinical manifestations and medication history described above, a diagnosis of immune-related peripheral neuropathy was made. In this case, the irAE severely hindered the treatment process and impaired the patient's quality of life. Through this case report and a review of the literature, we aim to explore how to timely and accurately identify irAEs in immunotherapy, especially nonspecific irAEs, and provide timely treatment to improve patient quality of life and survival and immunotherapy precision and safety.

Axillary surgery in breast cancer has undergone progressive de-escalation. The recent Sentinel Node versus Observation after Axillary Ultrasound (SOUND) and Intergroup Sentinel Mamma (INSEMA) trials have demonstrated that sentinel lymph node biopsy may be safely omitted in selected patients. This study aimed to evaluate the clinical relevance and applicability of the SOUND and INSEMA trial criteria within the Australian and New Zealand context.

Prospectively maintained data from the BreastSurgANZ Quality Audit (BQA) was analysed. Patients with invasive breast cancer treated between 2019 and 2023 who met the inclusion criteria of the SOUND and INSEMA trials were identified.

A total of 69 122 patients were treated for invasive breast cancer over the five-year study period, of whom 30 822 fulfilled the inclusion criteria of either the SOUND or INSEMA trials. Overall, 34.0% and 44.6% of patients with invasive breast cancer in Australia and New Zealand met the SOUND and INSEMA eligibility criteria, respectively. Tumour characteristics of BQA patients were more closely aligned with those reported in the SOUND trial than the INSEMA trial, although key differences in other clinicopathological features were observed.

The SOUND and INSEMA trial criteria are applicable to over one-third of patients with invasive breast cancer in Australia and New Zealand, supporting the potential relevance of axillary surgery de-escalation in this population.

Pulmonary neuroendocrine neoplasms (NENs) comprise a biological spectrum ranging from well-differentiated carcinoid tumors to poorly differentiated neuroendocrine carcinomas. In 2026, the International Association for the Study of Lung Cancer (IASLC) proposed an updated classification introducing pulmonary carcinoid/NET G3 as a distinct category of well-differentiated tumors with increased proliferative activity, incorporating Ki-67 into the diagnostic framework and aligning pulmonary NENs with other organ systems. However, the clinicopathological characteristics and prognostic significance of this newly proposed entity remain incompletely defined.

We conducted a retrospective single-center study of pulmonary neuroendocrine neoplasms diagnosed between 2007 and 2024. Clinical, histopathological, immunohistochemical, and survival data were collected. Tumors with well-differentiated morphology and increased proliferative activity were identified using predefined study criteria (mitotic count > 10/2 mm² and/or Ki-67 > 20 %). Following publication of the 2026 IASLC proposal, these tumors are referred to as carcinoid/NET G3 throughout the revised manuscript. RB1 and p53 immunohistochemistry was performed, and survival was analyzed using Kaplan-Meier estimates and Cox regression.

Among 155 pulmonary neuroendocrine neoplasms, eight (5.2 %) fulfilled criteria for carcinoid/NET G3. These tumors exhibited well-differentiated morphology despite elevated proliferative activity, retained RB1 expression, and a wild-type p53 immunophenotype, distinguishing them from LCNEC. Clinically, carcinoid/NET G3 showed an intermediate prognosis between conventional carcinoids and LCNEC. Mitotic count and Ki-67 demonstrated only moderate correlation, and Ki-67 identified additional biologically relevant tumors with relatively low mitotic activity.

Our findings provide independent clinicopathological validation of the recently proposed IASLC carcinoid/NET G3 concept. Integration of morphology, Ki-67, RB1 and p53 may improve diagnostic classification and prognostic stratification of pulmonary neuroendocrine neoplasms while supporting implementation of the emerging pulmonary carcinoid/NET G1-G3 framework.

The genus Eugenia comprises approximately 1050 species widely used in traditional medicine and human nutrition due to their diverse pharmacological properties. This review aimed to critically summarize the anticancer potential of Eugenia species and to correlate their biological activities with the presence of bioactive phytochemicals. Literature published between 2013 and 2025 was retrieved from PubMed, SciELO, and Google Scholar databases using terms related to Eugenia, cancer, antiproliferative, and cytotoxic activities. Increasing evidence has demonstrated the anticancer effects of selected Eugenia species in in silico, in vitro, and in vivo models against different cancer types. These effects are associated with multiple mechanisms, including apoptosis induction via caspase-3/7 activation and Fas receptor upregulation, inhibition of tumor cell migration and invasion through suppression of MMP-2 and MMP-9, and cell cycle arrest. The observed activities are closely related to the presence of flavonoids, phenolic acids, carotenoids, monoterpenes, triterpenes, and sesquiterpenes. Despite promising preclinical findings, limitations such as the scarcity of in vivo studies, lack of extract standardization, and absence of clinical trials still hinder the translational application of Eugenia-derived compounds in oncology. Future studies focusing on mechanistic elucidation, bioavailability, toxicity, and clinical validation are essential for the development of Eugenia-based anticancer therapies.

Multiple myeloma (MM) is a hematological malignancy with limited therapeutic options. Drug repurposing offers a pragmatic strategy to identify novel candidates, including those from Traditional Chinese Medicine (TCM). Here, a gene signature-guided repurposing approach was applied to transcriptomic data using Limma and weighted gene coexpression network analysis to define MM-associated hub genes, followed by diagnostic and prognostic evaluation. Coremine Medical screening identified Camellia sinensis root (CSR) and Ginkgo biloba leaves (GBL) as promising candidates. CSR and GBL extracts inhibited MM cell proliferation with IC₅₀ values of 1.54 mg/mL and 1.79 mg/mL, respectively, and induced G2/M cell cycle arrest with cyclin B1 downregulation. Apoptosis assays showed increased cell death and Bcl-2/Bax modulation. Wnt/β-catenin signaling was suppressed, correlating with cell cycle arrest and apoptosis. HPLC analysis revealed that CSR is rich in amino acids and flavanols, including L-theanine and epicatechin, while GBL contains flavonol glycosides and terpene lactones, such as quercetin, kaempferol, isorhamnetin, ginkgolide A-C, and bilobalide. These results indicate that CSR and GBL exert selective anti-myeloma activity via Wnt/β-catenin-mediated cell cycle arrest and apoptosis, highlighting their potential as repurposing candidates for MM.

The development of new therapeutic agents for glioblastoma and hepatocellular carcinoma (HCC) remains a priority due to poor prognosis, limited treatment options, and high recurrence rates. Herein, we report a one-pot synthesis of aromatic aminopropyl lactams (ArAPLs) via hydrolysis of bicyclic amidines (DBN, DBU), followed by reductive amination with aromatic aldehydes. These compounds were designed to target histamine H₃ receptors (H₃R), which are often overexpressed in these malignancies. Docking studies suggested that compounds 3a and 4a may act as H₃R antagonists, showing favorable binding through hydrophobic and hydrogen-bonding interactions. Biological evaluation identified 3a and 4a as the most promising compounds, exhibiting micromolar antiproliferative activity in glioblastoma and HCC cell models. Compound 3a showed the best balance between potency and selectivity, including activity in 3D spheroid models and modulation of cell cycle-related markers. In coculture systems, spheroids displayed reduced size and density, although a slight increase in viability was observed, particularly with 4a. Variations in peripheral cell layers suggest a role for macrophage behavior. Overall, these findings support the cytotoxic potential of ArAPLs, although further studies are required to confirm their role as H₃R antagonists.