Bladder cancer is a common urogenital malignancy that remains difficult to treat, particularly due to therapeutic resistance, such as resistance to cisplatin, in which cancer stem cells (CSCs) play a central role. This study investigates the combination of 5-aminolevulinic acid-mediated photodynamic therapy (5-ALA-PDT) and berbamine as a potential multimodal treatment strategy using the bladder cancer cell lines RT112 and J82, their cisplatin-resistant variants, and generated CSC-like cells. Berbamine is a natural plant compound and was confirmed in this study to have anticancer properties by inhibiting cell migration and invasion, and by inducing apoptosis. This study also showed that berbamine enhances the accumulation of protoporphyrin IX (PpIX), the photosensitizer induced by 5-ALA. 5-ALA-PDT destroys cancer cells by stimulating PpIX via 635 nm red laser light to produce reactive oxygen species (ROS). This was found to happen in all tested cell lines, whereas berbamine could modulate the cell destruction in a concentration-dependent manner and was influenced by the specific biological characteristics of the tested cell variants. CSCs showed the strongest response to the combination therapy approach, suggesting that they may represent more vulnerable cell variants to the tested treatment. Cisplatin-resistant cell lines could also be treated successfully with 5-ALA-PDT, whereas berbamine could enhance its efficacy in the cisplatin-resistant J82 LTT. These findings suggest that the combination treatment of 5-ALA-PDT and berbamine may serve as a promising approach to overcome therapeutic resistance in bladder cancer, particularly in cisplatin-resistant and CSC-enriched tumour types.

Approximately 70% of clear cell renal cell carcinoma (ccRCC) patients harbor von Hippel‒Lindau (VHL) deficiency, which drives pseudohypoxia and metabolic reprogramming. Here, we report a histone H4 lysine 12 lactylation (H4K12la)-fueled phosphoglycerate kinase 1 (PGK1)-lactate positive feedback loop that sustains glycolytic flux in VHL-deficient ccRCC and is pharmacologically disruptable by glucocorticoids. H4K12la is markedly elevated in ccRCC tissues and is associated with advanced pathological stage and unfavorable patient outcome. Integrative transcriptomic and epigenomic profiling revealed that VHL deficiency amplifies H4K12la deposition at accessible promoters, coupled to transcriptional activation of glycolytic and tumor-promoting programs, exemplified by PGK1. Through high-content drug screening, we identify glucocorticoids as effective suppressors of H4K12la, which act via glucocorticoid receptor-mediated transcriptional repression of glycolytic genes and consequent attenuation of lactate production. Strikingly, VHL-deficient ccRCC exhibits greater on-target pathway sensitivity to dexamethasone at the H4K12la-glycolysis axis, and glucocorticoid dexamethasone potentiated the antitumor efficacy of the HIF-2α inhibitor belzutifan in both orthotopic cell line-derived and patient-derived xenograft models. Collectively, our findings establish H4K12la as a metabolic‒epigenetic amplifier in VHL-deficient ccRCC, reposition glucocorticoids as epigenetically active modulators that dampen lactate-driven chromatin activation and glycolytic output, and provide a mechanistically grounded combination strategy with HIF-2α blockade to target lactate-fueled transcriptional dependence in metabolically rigid tumors.

Lung resection is a standard treatment for localized lung cancer, but prolonged air leakage is a common complication with health and economic burdens. Interventions such as staplers, sealants, and adjunctive materials are used, yet real-world data describing their utilization remain limited.

We report a case of Hodgkinoid histiocytosis (HH) with protracted skin manifestations. A 72-year-old Japanese woman presented with fever of unknown origin, lymphadenopathy, eosinophilia, and a generalized pruritic and erythematous maculopapular rash. Biopsy of an inguinal lymph node indicated a proliferation of large cells with clear cytoplasm, mimicking Hodgkin lymphoma (HL). Immunohistochemical analysis showed that the Hodgkin-like cells were positive for S-100 protein and CD30 but negative for langerin, CD20, PAX5, and CD3. The cells were also positive for PD-L1. The histological findings were similar to those of HL; conversely, immunohistochemical results suggested a histiocytic/dendritic cell origin. Therefore, the patient was diagnosed with HH. Systemic corticosteroid therapy markedly improved her systemic manifestations; nonetheless, cutaneous symptoms persisted. Drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) was suspected because of the prolonged cutaneous manifestations, and the diagnostic criteria for these conditions were fulfilled. Discontinuation of the culprit drug resulted in the remission of cutaneous symptoms. Because lymph node lesions in DIHS/DRESS also demonstrate HL-like histology, this case suggests that HH, while a novel and distinct histiocytic/dendritic cell disorder, may be associated with lymph nodal lesions occurring in the context of DIHS/DRESS.

Primary gastrointestinal lymphoma accounts for only 1-4% of all gastrointestinal malignancies, yet the gastrointestinal tract is the most common extranodal site of non-Hodgkin lymphoma, comprising 10-15% of all non-Hodgkin lymphomas. Among these, diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue lymphoma frequently affect the stomach and small intestine. Protein-losing enteropathy associated with malignant lymphoma is exceedingly rare, particularly when caused by CD5-positive DLBCL. We report the case of a 60-year-old woman with a four-year history of refractory diarrhea and progressive lower extremity edema, ultimately diagnosed with CD5-positive DLBCL of the small intestine. Diagnostic workup revealed hypoproteinemia with significant protein leakage in the ascending colon and distal small intestine. Double-balloon endoscopy demonstrated shallow, wide ulcers with patchy whitish exudates, and histopathology confirmed a diagnosis of de novo CD5-positive DLBCL. Chemotherapy with rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH-R) led to prompt improvement in serum albumin levels and resolution of the protein-losing enteropathy. Subsequent high-dose chemotherapy with autologous stem cell transplantation has maintained remission. Given the rarity of this presentation and its strong similarity to a previously reported case of CD5-positive DLBCL with protein-losing enteropathy, we propose that this might represent a distinct clinical entity.

To clarify the karyotype evolution of multiple myeloma (MM), multiple karyotypes of 22 patients with MM were analyzed using G-banding, and their karyotype evolutions were depicted as phylogenetic trees. Eleven patients exhibited highly complex karyotype evolutions, combining branched evolution, linear evolution, parallel evolution and macroevolution. While chromosomal structural abnormalities involving 14q32 were detected at the roots of the phylogenetic trees of karyotype evolution, aneuploidies and the other structural abnormalities were identified in both the initial clones and karyotypically evolved subclones. The findings indicated that aneuploidies might be caused by unequal chromosomal segregation, loss of the chromosome with unbalanced whole-arm translocation, and whole-chromosome doubling in patients with near-tetraploidy. Four patients had karyotype abnormalities (three del(20)(q) and one del(5)(q)) associated with myelodysplastic syndrome independent of the karyotype evolution of MM. In conclusion, the phylogenetic trees depicted by G-banding present the karyotype evolution of MM.

Peritoneal metastasis (PM) from gastric cancer (GC) is associated with poor prognosis and limited treatment options. We investigated a novel peritoneal-targeted therapy using CF33-human sodium iodide symporter (hNIS), a chimeric orthopoxvirus, combined with anti-PD-L1 immune checkpoint blockade in an immunocompetent mouse model of GCPM.

Insufficient T-cell infiltration limits the effectiveness of immunotherapy in sarcoma, yet the tumor-intrinsic mechanisms that govern immune exclusion remain poorly defined.

Immune checkpoint inhibitors (ICIs) therapy targeting programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) shows promising clinical benefits in non-small cell lung cancer (NSCLC). However, the relatively low response rate highlights the need to elucidate the regulatory mechanism of PD-L1 expression, and develop an alternative strategy to target PD-1/PD-L1 immune checkpoint pathway. Our study focuses on the role and mechanism of ubiquitin-specific protease 15 (USP15) and its derived peptide U10 on NSCLC immune evasion.

Survival outcomes for early-stage breast cancer have improved substantially; however, many survivors experience persistent treatment-related toxicities that adversely affect long-term quality of life (QoL) and functional recovery. Prospective survivorship data from China remain limited. The PERSEVERE study aims to characterise longitudinal trajectories of QoL and treatment-related toxicities among Chinese women treated for stage I-III breast cancer and to identify factors associated with suboptimal recovery.

Hepatocellular carcinoma (HCC), a prevalent malignant tumor, is characterized by occult early symptoms, leading to most patients being diagnosed at advanced stages. This diagnostic delay significantly contributes to the high mortality and limited therapeutic efficacy observed in HCC. Therefore, the development and application of accurate early detection methods and efficacious treatment strategies are essential for improving patient survival and overall clinical outcomes. Glycoproteomics focuses on the characterization of glycosylation sites and site-specific glycans. As one of the most prevalent post-translational modifications of proteins, aberrant glycosylation plays a critical role in the initiation, progression, diagnosis and treatment of HCC. In-depth investigation of abnormal glycoproteins in HCC holds substantial scientific and clinical significance for unraveling its pathogenesis, identifying effective diagnostic biomarkers, and pinpointing potential therapeutic targets. Body fluids and the derived exosomes have emerged as a pivotal research frontier, owing to their distinctive advantages: non-invasiveness, a wealth of disease-associated information, and ease of collection. Based on this, this review elaborates on the research strategies of HCC glycoproteomics and provides a detailed description of the analysis of body fluids and derived exosomes, to explore potential biomarkers in the pathogenesis of HCC, thereby providing strong support for the early detection and personalized treatment.

We present the first metastatic castration-resistant prostate cancer (mCRPC) patient, heavily pretreated with multiple systemic and radioligand therapies, who received [212Pb]Pb-PSMA radioligand therapy (PRLT) combined with the metabotropic glutamate receptor (mGluR)-inhibitor Riluzole due to disease progression. This novel combination, aimed at targeting glutamine addiction in prostate cancer and exploiting radio-sensitization, was well tolerated leading to partial remission of the disease, decrease in PSA values, and stability of symptoms. This represents the first-in-human clinical application of [212Pb]Pb-PSMA PRLT combined with mGluR inhibition in mCRPC, representing a promising therapeutic strategy for advanced, treatment-refractory, progressing patients, supported by molecular imaging and clinical benefit.

A 79-year-old patient with a history of renal cell carcinoma (RCC) presented with nonspecific upper abdominal pain 6 months ago. Contrast-enhanced CT and MRI did not reveal definitive evidence of malignancy. However, 68Ga-LNC1007 (68Ga-FAPI-RGD) PET/CT demonstrated a significant radiotracer-avid focus in the tail of the pancreas, initially interpreted as a metastatic RCC lesion. Surgical pathology later confirmed the lesion as a neuroendocrine neoplasm (NEN). This case illustrates that neuroendocrine tumors may occasionally be missed by conventional imaging modalities or suspected as other malignancies in certain scenarios, and highlights the potential diagnostic value of 68Ga-LNC1007 PET/CT in detecting neuroendocrine tumors.

A 51-year-old woman presented with intermittent upper abdominal pain for two years and unintentional weight loss recently. Gastroscopy revealed a large cardia mass protruding into the gastric lumen. CT examination suggested malignant gastric tumor. Subsequently, ¹⁸F-FDG PET/CT demonstrated heterogeneous intense uptake in the gastric mass. Pathologic examination identified a gastric pyloric gland adenoma by immunohistochemistry. The lesion was resected locally, and the patient recovered well.

A 57-year-old woman presented with fever was incidentally found to have a large hepatogastric space mass with coarse calcifications on CT, accompanied by a markedly elevated serum CA-125 level (3082 U/mL). 18F-FDG PET/MR revealed intense metabolic activity (SUVmax= 10.82) and restricted diffusion without ascites, while both ovaries appeared unremarkable. Pathology confirmed primary peritoneal high-grade serous carcinoma (PPHGSC). This case illustrates atypical imaging features of this rare malignancy, including lesion localization, coarse calcification, and absence of ascites.

Fibroblast activation protein (FAP) has emerged as a promising molecular target for theranostic strategies. Here is a case of a 37-year-old woman with poorly differentiated pancreatic adenocarcinoma with lymph node metastasis who received 1 cycle of gemcitabine plus nab-paclitaxel, but relapsed a year ago. She then received 3 cycles of 177Lu-FAP-2286 treatment, in combination with 6 cycles of gemcitabine plus nab-paclitaxel therapy. After that, the patient received an additional 2 cycles of 225Ac-FAP-2286 treatment. A follow-up 68Ga-FAP-2286 PET/CT scan revealed complete metabolic response of the lesions, and no severe adverse reactions were reported.

Primary splenic angiosarcoma is a rare, aggressive malignancy carrying a poor prognosis. A 65-year-old woman with a pathologically confirmed well-differentiated splenic angiosarcoma developed liver metastases 5 months into follow-up. Subsequent 18F-FDG and 68Ga-FAPI PET/CT imaging revealed a "dual-negative" pattern, demonstrating no significant radiotracer uptake in the metastatic liver lesions. Despite well-differentiated histology, the tumor showed rapid progression, confirming aggressive behavior in well-differentiated angiosarcoma. The high-grade splenic angiosarcoma demonstrated negative findings on dual-tracer PET/CT, underscoring that vigilance and comprehensive multimodal evaluation are crucial for such occult malignancies.

Cancer-associated fibroblasts (CAFs) represent a predominant cell population in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC). How the spatial distribution of CAF subtypes relates to immune modulation within the TME remains incompletely understood. This study aimed to characterize the spatial organization of CAF subtypes in HCC and to explore their potential associations with immune contexture.

Mucosal melanoma (MM), an aggressive melanoma subtype arising in mucosal tissues, displays resistance to therapies effective in cutaneous melanoma. To understand how mucosal microenvironment contributes to treatment nonresponsiveness, we performed integrative analysis of single-cell and bulk messenger RNA sequencing data derived from oral mucosa-originated melanoma and revealed that mucosa-specific inflammation induces enrichment of low-pigmented neural crest-like cancer cell, mediated by COX2+ macrophages and their secretome. Maintenance of this inflammation-induced neural crest-like state in cancer cells depends on HER2 and HER3 activation. Inhibition of HER2/3 by pan-HER inhibitors blocks cell state plasticity and overcomes chemoresistance in primary MM cell lines and patient-derived xenograft (PDX) models. These findings provide insights into how the tissue of origin determines cancer aggressiveness, highlight the role of mucosal inflammation in driving melanoma stemness and chemoresistance, and advance the identification of effective treatment options currently lacking for patients with MM.

Altered cell-surface glycans are established cancer biomarkers, yet no oncogenes have been identified within glycan biosynthesis machinery. This represents a critical gap, as defining a gene as a true oncogene, rather than merely a component of an oncogenic pathway, reveals targetable dependencies that can improve clinical decisions. To date, no gain-of-function mutations have been detected in glycogenes, and the search for such mutations is largely saturated. To address this gap, we developed a bioinformatic-experimental pipeline to identify copy number alteration (CNA)-based driver genes, overcoming noise from passenger genes. The approach recovered known oncogenes and tumor suppressors, while revealing novel candidates, including glyco-oncogenes. Focusing on the glycosphingolipid (GSL) biosynthetic pathway, we validated B4GALT5 as a bona fide glyco-oncogene whose genomic amplification drives proliferation, oncogene addiction, and poor prognosis, effects that can be reversed by targeted pathway inhibition. Mechanistic studies show that B4GALT5 promotes cancer cell survival via integrin-Src signaling under anchorage-independent conditions. Collectively, these findings establish glycosylation enzymes as a druggable oncogene class and provide a resource of high-confidence CNA-based cancer regulatory genes.