Primary pulmonary B-cell lymphomas are rare, accounting for <1% of non-Hodgkin lymphomas (NHLs) and 3-4% of extranodal NHL. Extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT; pulmonary MALT lymphoma), arising from bronchus-associated lymphoid tissue (BALT), represents over 80-90% of cases. These tumors typically develop as a result of chronic antigenic stimulation in the setting of persistent inflammation, due to infection, or autoimmune disease. Two main pathogenetic phases are recognized in their development: an antigen-dependent phase, in which clonal B-cell expansion and survival are driven by ongoing exposure to specific antigens, and an antigen-independent phase, in which B-cell proliferation becomes autonomous due to cytogenetic and molecular alterations. Clinically, pulmonary MALT lymphoma has an indolent course and is often detected incidentally; when symptoms occur, they are non-specific. Radiologic findings include consolidations, nodules, or masses. Diagnosis relies on histopathology, immunophenotyping (CD20+, light-chain restriction, CD5-/CD10-/cyclin D1-), and molecular studies. Most patients present at early Ann Arbor stages, with a 5-year overall survival exceeding 90%. Management should be tailored to the disease stage, symptoms, comorbidities, and patient preferences. A watch-and-wait approach is appropriate for asymptomatic patients without treatment indications. Radiotherapy is highly effective for localized disease, while rituximab alone or with chemotherapy, particularly bendamustine-rituximab, is preferred for advanced symptomatic disease. Bruton's tyrosine kinase inhibitors have shown efficacy in relapsed or refractory cases. This review summarizes the epidemiology, pathogenesis, clinicopathologic features, diagnosis, and evolving treatment strategies of pulmonary MALT lymphoma, highlighting its favorable prognosis and unique immunobiological origin.
BACKGROUND AND OBJECTIVE:Patient-derived organoids (PDOs) are emerging as powerful ex vivo models for studying ovarian cancer (OC) biology and drug response. However, success rates for establishing OC PDOs remain low, partly due to heterogeneous media formulations and inconsistent definitions of "success". This review aims to compare media compositions, summarize derivation efficiencies across studies, and identify cross-cancer insights that may inform optimization of OC PDO culture conditions. METHODS:A structured PubMed search was performed using the terms "ovarian cancer PDOs" and "ovarian cancer patient-derived organoids". Studies were included if they were primary research articles, published from 2018 onward, did not use commercial PDO kits, and provided detailed descriptions of media composition and culture methods. Ten studies met all criteria and were analyzed for media components, tissue sources, derivation efficiencies, and definitions of success. KEY CONTENT AND FINDINGS:Across 10 foundational studies, success rates ranged from 13% to 65%, influenced by tissue type, histology, and variable definitions of success. Media compositions shared core components such as advanced DMEM/F12, B27, GlutaMAX, nicotinamide, and A83-01, but differed significantly in Wnt/BMP modulators, growth factors, hormonal additives, and inhibitors. Evidence suggests that high-Wnt conditions support PDOs in colorectal and pancreatic cancers but may hinder long-term growth in HGSOC. Cross-cancer comparisons highlighted potentially transferable strategies, particularly from TP53-mutant pancreatic and colorectal PDO systems. CONCLUSIONS:OC PDO establishment remains challenging due to inconsistent culture conditions and varying success definitions. Standardizing media formulations, harmonizing reporting practices, and applying insights from other TP53-mutant cancers may improve reproducibility and clinical applicability. Tailored, subtype-specific optimization is likely necessary to enhance PDO derivation and utility in precision oncology.
BACKGROUND:The coexistence of a germline BRCA1 mutation and human epidermal growth factor receptor 2 (HER2)-positive breast cancer is rare and represents a distinct clinical and therapeutic challenge. The mechanisms underlying this association remain unclear. The HER2-positive subtype is associated with a more aggressive clinical course, but responds well to targeted anti-HER2 therapy, including trastuzumab. Although trastuzumab therapy is generally well tolerated, rare but potentially serious organ complications may occur. CASE DESCRIPTION:We report the case of a 41-year-old woman with a germline BRCA1 mutation and HER2-positive breast cancer who underwent bilateral mastectomy, removal of the ovaries and systemic treatment including chemotherapy and trastuzumab therapy. During treatment, she developed a marked elevation of liver enzymes consistent with drug-induced liver injury. After initial clinical improvement, she developed acute pancreatitis without biliary or metabolic causes, suggesting possible treatment-related toxicity. The clinical course was further complicated by Clostridioides difficile infection, likely associated with prior antibiotic exposure and immunosuppressive therapy. Following temporary interruption of systemic treatment and supportive management, the patient improved and was able to continue oncological therapy under close biochemical monitoring. CONCLUSIONS:This case highlights the potential for rare but serious multi-organ complications during trastuzumab-based therapy. Early recognition and appropriate management of such complications may allow continuation of oncological treatment. The case also emphasizes the need for further research on targeted therapeutic strategies, such as PARP inhibitors, for patients with HER2-positive, BRCA1-mutated breast cancer.
BACKGROUND AND OBJECTIVE:Biliary neuroendocrine tumors (NETs) are exceedingly rare malignancies that differ substantially from more common biliary tract cancers such as cholangiocarcinomas. Recent advances in imaging, pathology, and systemic therapies have prompted a re-evaluation of their clinical management. As research on these tumors grows, a clear and standardized synthesis of emerging evidence is necessary to guide clinicians and inform future investigations. In this article we summarized and critically discuss current knowledge on biliary tract NETs, with the aim of providing a structured narrative review that enhances understanding of their epidemiology, therapeutic approaches, and clinical outcomes. METHODS:This narrative review of the literature integrates findings from searches of electronic medical databases, manual reference checks, and authoritative clinical and pathological sources to gather contemporary data on the incidence, diagnostic modalities, treatment strategies, and prognostic factors for biliary NETs. KEY CONTENT AND FINDINGS:Current evidence on biliary NETs is examined, including global epidemiologic trends, diagnostic challenges, advances in imaging and histopathological classification, and evolving therapeutic options such as surgery, systemic therapy, and loco-regional treatments. Practical implications for multidisciplinary management are highlighted, with emphasis on how recent data may influence clinical decision-making and patient outcomes. CONCLUSIONS:Biliary NETs are a biologically heterogeneous and rare group of neoplasms. The present management guidelines are largely based on the larger gastrointestinal endocrine tumor (GEP-NET) literature, due to the lack of prospective biliary-specific clinical trials. Localized, well-differentiated lesions can only be cured by surgical resection, but high-grade neuroendocrine carcinomas require platinum-based systemic therapy. Future research must focus on holistic molecular characterization, the development of multicenter registries and the conduct of site-specific therapeutic trials to augment the accuracy of evidence-based clinical practice.
BACKGROUND AND OBJECTIVE:Differentiating glioma recurrence from radiation necrosis remains a critical diagnostic challenge in neuro-oncology due to overlapping imaging features. Positron emission tomography (PET) and magnetic resonance imaging (MRI) offer complementary metabolic and structural information that may enhance diagnostic accuracy. This narrative review evaluates the performance of PET, advanced MRI techniques, and their integration in distinguishing tumour recurrence from post-treatment effects. METHODS:A comprehensive search of PubMed, Medline, and Embase databases was conducted to identify studies published after April 2020. Inclusion criteria comprised studies on histologically diagnosed gliomas using PET and MRI, reporting sensitivity, specificity, or accuracy. KEY CONTENT AND FINDINGS:Eight cohort studies met the inclusion criteria, examining PET tracers (18F-FDG, 18F-FET, 11C-MET, 18F-DOPA) and advanced MRI techniques [diffusion kurtosis imaging (DKI), dynamic susceptibility contrast (DSC) perfusion, magnetic resonance spectroscopy (MRS)]. The integration of PET and MRI outperformed standalone modalities in diagnostic accuracy in all but one study. 18F-FET PET demonstrated high diagnostic accuracy, with sensitivity up to 95% and no diagnostic improvement when combined with MRI in high-grade glioma, though its availability remains limited. MRI alone had variable sensitivity (33-77%) and specificity (50-100%), depending on the technique and tracer used. DKI showed promise in enhancing sensitivity (72-100%). Heterogeneity in protocols and patient cohorts limited direct comparisons across studies. CONCLUSIONS:The combination of PET and MRI provides a superior diagnostic approach for differentiating glioma recurrence from radiation necrosis, with 18F-DOPA PET and advanced MRI sequences emerging as the most effective pairing. Further multicenter studies with standardized protocols are required to validate these findings and address challenges related to tracer accessibility and protocol variability. These advancements have the potential to optimize patient management in neuro-oncology.
BACKGROUND:Sijunzi decoction (SJZD) is a traditional Chinese medicine (TCM) commonly used for pancreatic ductal adenocarcinoma (PDAC), but its mechanisms remain unclear. This study investigates its molecular basis using network pharmacology and molecular docking. METHODS:Active compounds and targets of SJZD were identified via Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform, and PDAC-related targets were retrieved from Online Mendelian Inheritance in Man (OMIM) and GeneCards. Protein-protein interaction (PPI) networks, Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and tissue distribution analyses were conducted. Molecular docking evaluated binding affinities between compounds and targets. The anti-PDAC effects of SJZD were evaluated in vitro using human pancreatic cancer cell lines (CFPAC-1 and MiaPaCa-2) and in vivo using a patient-derived xenograft (PDX) mouse model. RESULTS:SJZD comprises 131 compounds and 260 targets, with key targets such as AKT serine/threonine kinase 1 (AKT1), BCL2 associated agonist of cell death (BAD), BCL2 apoptosis regulator (BCL2), and tumor protein p53 ( TP53) identified through PPI analysis. Enrichment analyses highlighted the phosphatidylinositide 3-kinases (PI3K)/protein Kinase B (AKT)/mechanistic target of rapamycin kinase (mTOR) and apoptosis pathways as primary therapeutic mechanisms. SJZD exhibited cytotoxic effects against PDAC cells in vitro and suppressed tumor growth in vivo, with mechanistic analyses confirming its regulatory effects on the PI3K/AKT/mTOR and apoptosis pathways. Molecular docking revealed strong binding affinities, particularly for compounds targeting estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2). These findings suggest that SJZD exerts anti-PDAC effects via multi-target modulation, primarily through inhibition of the PI3K/AKT/mTOR signaling axis, induction of apoptosis and autophagy, and anti-inflammatory activity. The involvement of classic compounds supports the rationale of its traditional use, while experimental validation provides a mechanistic foundation for future clinical development. CONCLUSIONS:This study clarifies the active components, targets, and mechanisms of SJZD in treating PDAC, offering insights into the therapeutic potential of TCM.
BACKGROUND:Trifluridine/tipiracil (TAS-102) and regorafenib are approved and widely utilized as later-line treatment options for patients with metastatic colorectal cancer (mCRC). However, the optimal sequence between these agents remains unclear. We conducted a systematic review and meta-analysis to compare the efficacy and safety of two treatment sequences: TAS-102 followed by regorafenib (TR) versus regorafenib followed by TAS-102 (RT) in patients with mCRC who had previously failed chemotherapy. METHODS:This study was registered with PROSPERO (CRD42024622437). We systematically searched six databases (PubMed, Scopus, CINAHL, ScienceDirect, medRXiv, and OpenGrey) up to June 1, 2025. Risk of bias was assessed using the ROBINS-I tool. Pooled estimates with 95% confidence intervals (CIs) were calculated using a random-effects model. For studies lacking hazard ratios (HRs), we estimated the HRs using the ratio of median survival times. Publication bias was evaluated with a funnel plot. RESULTS:Thirteen observational studies with moderate to critical risk of bias were included. No significant difference was found in overall survival (OS) (HR =1.04, 95% CI: 0.86-1.25, I2=72%) or progression-free survival (PFS) (HR =1.34, 95% CI: 0.77-2.34, I2=92%) between the TR and RT groups. The RT group had a higher disease control rate (DCR) (33.1% vs. 28.0%) and tended to have more adverse events (AEs). CONCLUSIONS:OS and PFS outcomes were comparable between patients treated with TAS-102 followed by regorafenib and those receiving the reverse sequence. Although the RT group was associated with a slightly higher DCR, this was accompanied by a trend toward increased AEs.
BACKGROUND:Chronic gastritis affects ~50% of the population, frequently linked to Helicobacter pylori (H. pylori). Fos-related antigen 1 (FRA-1) has been reported to be involved in stomach inflammation and malignancy. The study aimed to investigate the regulatory role of FRA-1 in H. pylori-induced inflammatory response of gastric epithelial cells, and to explore its mechanism and application prospect of FRA-1 in H. pylori infection treatment. METHODS:GES-1 cells were selected to knock down the level of FRA-1 by specific small interfering RNA (siRNA) prior to H. pylori infection. The messenger RNA (mRNA) expression of FRA-1 and cytokines was quantified by real-time quantitative polymerase chain reaction (RT-qPCR), protein levels were analyzed by western blot, and cytokine secretion was measured by enzyme-linked immunosorbent assay (ELISA). Nuclear factor-κB (NF-κB) activity was then assessed by western blot and immunofluorescence. RESULTS:It was showed that infection with H. pylori markedly increased FRA-1 expression levels. Knockdown analysis identified that FRA-1 was required for H. pylori-induced inflammatory cytokines expression in GES-1 cells. In addition, FRA-1 exerted proinflammatory response to H. pylori by augmenting NF-κB activation. CONCLUSIONS:This work suggests a key function for FRA-1 in underlying the inflammatory pathology of H. pylori-associated gastritis, and that it could serve as a useful detection indicator and therapeutic target.
BACKGROUND:Early hepatocellular carcinoma (HCC) remains difficult to diagnose because of its insidious and asymptomatic onset. Liquid biopsy provides a promising non-invasive approach for early tumor detection. 5-Hydroxymethylcytosine (5-hmC), the oxidation product of 5-methylcytosine (5-mC), has emerged as an informative epigenetic mark reflecting tumor-associated alterations during hepatocarcinogenesis. This study aimed to identify and validate a circulating cell-free DNA (cfDNA) 5-hmC-based signature for the early detection of HCC and to evaluate its diagnostic and prognostic potential. METHODS:Using an XGBoost-based ensemble learning framework, we identified cfDNA 5-hmC markers that defined an early HCC 5-hmC signature. The signature was assessed in training and validation cohorts using receiver operating characteristic (ROC) analysis, with the area under the curve (AUC) as the primary performance metric. RESULTS:We defined a 19-gene cfDNA 5-hmC signature (eHMS), which showed high diagnostic accuracy for early HCC across multiple precancerous states, with AUCs of 92.3% (healthy controls vs. early HCC), 82.5% [benign liver lesions (BLL) vs. early HCC], 78.8% [chronic hepatitis B (CHB) vs. early HCC], 81.3% (liver cirrhosis vs. early HCC), and 89.4% when pooling all non-HCC, further validated in an external cfDNA cohort (AUC =93.5%). When traced to tissue 5-mC, the 5-mC-related eHMS (MeHMS) score distinguished tumors from adjacent tissues with an AUC of 99.9% and showed improved discriminatory performance compared with alpha-fetoprotein (AFP, AUC =71.5%). Moreover, the signature may reflect early metabolic reprogramming and provide prognostic value by stratifying patients for survival and disease progression. CONCLUSIONS:Our findings indicate that the eHMS represents a promising biomarker for liquid biopsy in early HCC surveillance.
BACKGROUND:Early-onset colorectal cancer (EO-CRC) has been gaining momentum in the oncologic community and has a reputation for being overtreated. Neoadjuvant therapy has been proven to be an effective treatment for rectal cancers; however, treatment outcomes in this group have yet to be studied. The purpose of this study was to compare overall survival (OS) between the upfront surgery (UFS) group and the neoadjuvant chemotherapy (NAC) group in EO-CRC. METHODS:A retrospective analysis was conducted on 162 patients with stage III-IV locally advanced EO-CRC who underwent radical surgery at a single centre between January 2018 and December 2023. Baseline characteristics, treatment modalities, pathological findings, metastasis, recurrence and survival outcomes, disease-free survival (DFS) and OS, were compared. Survival was assessed using Kaplan-Meier analysis and Cox regression. Propensity score matching (PSM) was performed to adjust for baseline differences. RESULTS:Baseline demographics were broadly similar except for higher abdominal pain frequency in UFS (42.1% vs. 17.2%, P=0.01). NAC was associated with greater rectal tumor proportion (75.9% vs. 43.6%, P=0.002) and higher pathological downstaging after matching (23/45 vs. 22/45, P=0.001). Survival analyses revealed improved DFS (P=0.005) and OS (P=0.001) with NAC, along with reduced recurrence (P=0.001). Multivariate analysis identified preoperative stage, nodal status, invasion, and metastases as key survival predictors; NAC was not an independent predictor. CONCLUSIONS:In EO-CRC, NAC achieves tumour downstaging and survival benefits compared to UFS. These findings support the integration of NAC into multimodal treatment strategies to improve oncologic outcomes in selected patients. Larger prospective studies are needed.
BACKGROUND AND OBJECTIVE:Intravesical instillation of chemotherapeutic drugs remains a cornerstone in the management of non-muscle-invasive bladder tumor following transurethral surgery, where they are routinely employed to prevent disease recurrence and progression. In patients with locally advanced or metastatic urothelial carcinoma, cisplatin-based combination chemotherapy continues to represent the standard systemic treatment and has also been used in the neoadjuvant setting prior to radical cystectomy. Despite these established strategies, a substantial proportion of these patients exhibit intrinsic or acquired resistance to chemotherapeutic regimens, ultimately leading to poor oncologic outcomes, although the molecular mechanisms underlying chemoresistance remain only partially understood. Meanwhile, accumulating evidence has increasingly suggested a critical role of androgen receptor (AR) signaling in promoting not only the development and progression of urothelial cancer but also resistance to conventional non-surgical therapy for bladder cancer. In this review article, we aim to summarize available data suggesting that AR is involved in chemosensitivity in urothelial cancer. METHODS:We searched five scholarly databases [PubMed, Embase, Scopus, Google Scholar, and World Health Organization (WHO) Global Index Medicus], using the relevant keywords variably combined. Studies published in English from January 1950 to January 2026 were considered. KEY CONTENT AND FINDINGS:This article focuses on synthesizing current knowledge regarding the involvement of AR in modulating the efficacy of chemotherapeutic agents used for bladder cancer and discusses their potential of overcoming chemoresistance. Several potential downstream effectors of AR signaling, which increase or decrease chemosensitivity, have also been identified. CONCLUSIONS:Available data may indicate that therapeutic strategies incorporating anti-AR therapy, apart from its direct anti-tumor activity, may hold considerable promise as a sensitizer of chemotherapy in patients with urothelial cancer.
BACKGROUND:The emergence of acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) presents a significant obstacle in the therapeutic strategy for EGFR-mutant non-small cell lung cancer (NSCLC). While secondary mutations explain some cases, adaptive resistance mechanisms involving lineage plasticity and metabolic rewiring are increasingly recognized but poorly understood. This study aimed to investigate the role of the transcription factor TP63 in mediating adaptive resistance to EGFR-TKIs, with a focus on its potential regulation of ferroptosis. METHODS:To investigate these mechanisms, we generated osimertinib-resistant derivatives of EGFR-mutant PC9 and HCC827 cell lines. We utilized short hairpin RNA (shRNA) interference to silence TP63 and performed functional assays including cell viability, colony formation, wound-healing, and transwell invasion assays. Mechanistic insights were gained through integrated RNA sequencing (RNA-seq), immunofluorescence, and lipid peroxidation assays using BODIPY 581/591 C11. RESULTS:We identified the transcription factor TP63 as a master regulator of adaptive resistance, showing marked upregulation in resistant cells. Although TP63 depletion did not affect basal cell viability, its loss significantly restored sensitivity to osimertinib, suppressing proliferation, clonogenic growth, and invasive potential. Transcriptomic and biochemical analyses revealed that TP63 maintains redox homeostasis by transcriptionally activating GPX4 and antioxidant gene networks. Consequently, TP63 silencing collapsed this defense system, leading to the accumulation of lipid peroxides and inducing ferroptotic cell death under drug pressure. CONCLUSIONS:Clinically, high TP63 expression correlates with reduced overall survival in EGFR-mutant NSCLC patients. These findings define a critical TP63-GPX4 ferroptosis axis that safeguards tumor cell survival during therapeutic stress, highlighting ferroptosis induction as a potential therapeutic strategy to overcome EGFR-TKI resistance.
