The present study aimed to establish patient-derived organoid (PDO) and patient-derived xenograft (PDX) models from clinical gastric cancer (GC) tissue samples and analyze their drug sensitivity data to evaluate their translational value in GC research. The present study investigated the integrated construction of PDOs and PDXs from the same patient and evaluated their utility in individualized drug sensitivity prediction and clinical translation.

By constructing GC PDOs and PDXs, drug sensitivity assays with multiple agents were performed and validated results against clinical therapeutic responses. Endoscopic and surgical GC specimens were synchronously processed to generate paired PDO and PDX models from identical patient tissues. Model fidelity was validated using hematoxylin and zeosin (H&E) staining, immunohistochemistry (IHC) and short tandem repeat (STR) profiling. In vitro drug sensitivity testing and in vivo PDX pharmacodynamic validation were performed and predicted outcomes were compared to clinical treatment responses.

The findings demonstrated that PDOs and PDXs effectively preserve key histopathological and genetic features of the original tumors, with high concordance between drug sensitivity profiles and actual clinical outcomes, providing a platform for precision therapy in GC. Both PDOs and PDXs recapitulated the histological features of primary tumors. IHC confirmed their consistency with the original tissue profiles, while STR analysis demonstrated >90% genetic matching between the models and the source tissues. The integrated PDO-PDX platform showed a high correlation in predicting drug sensitivity.

The integrated PDO-PDX platform achieved clinical concordance in predicting drug sensitivity, providing a platform for precision therapy in GC.

Patients with familial adenomatous polyposis (FAP) can develop multiple adenomatous polyps in the gastrointestinal tract, including the duodenum and large intestine. Few studies have reported surgical techniques for pancreaticoduodenectomy (PD) after prophylactic colorectal surgery, although this is technically challenging.

We describe the surgical technique used in a 46-year-old man with FAP who underwent PD for a papillary adenoma after prophylactic total colectomy. After resection of the specimen, the jejunal limb was elevated via the Treitz route (retro-remnant mesocolic plane) for pancreaticojejunostomy and hepaticojejunostomy. Subsequently, gastrojejunostomy was performed via an isoperistaltic route. To the best of our knowledge, this is the first study to present the technical aspects of PD after total colectomy, focusing on the jejunal limb route during reconstruction.

The present study highlights the clinical course of a patient who underwent PD after prophylactic total colectomy for FAP. As a functional mesocolic plane is absent in patients who have undergone prophylactic total colectomy, special considerations of the jejunal limb route are required in PD after prophylactic colorectal surgery. This approach may be an optional and feasible strategy for successful PD after prophylactic colorectal surgery.

Clear cell renal cell carcinoma (ccRCC) is the predominant subtype of renal cancer with poor prognosis at advanced stages. The ErbB receptor family, including HER2, EGFR, and ErbB3, is implicated in tumor progression through membrane signaling and nuclear functions, but their roles in ccRCC remain incompletely understood.

We analyzed membrane and nuclear expression of HER2, EGFR, and ErbB3 in ccRCC tissue samples by immunohistochemistry. Pearson correlation analyses evaluated receptor co-expression, while in vitro assays with HEK293 and 786-O cells treated with heregulin assessed nuclear localization. Clinical relevance was investigated by correlating receptor expression with Fuhrman Nuclear Grade and clinical stage using Fisher's exact test.

Membrane expression of HER2 and EGFR was positive in approximately 32% and 38% of cases, respectively, showing a significant positive correlation (r=0.3519, p=0.028). Nuclear expression was higher for EGFR and ErbB3, with HER2 nuclear presence correlating significantly with both receptors (r=0.4713 and r=0.42; p=0.001). In vitro, heregulin stimulation induced nuclear translocation of HER2 and ErbB3. Not funding that membrane and nuclear expression co-expression of HER2/EGFR was linked to clinical parameters. However, the nuclear co-expression of HER2/ErbB3 showed significant associations with higher FNG and advanced clinical stage (p<0.05).

Nuclear co-expression of HER2 with ErbB3 is frequent in clear cell renal cell carcinoma and is significantly associated with higher Fuhrman Nuclear Grade and advanced clinical stage. These findings indicate that nuclear ErbB signaling contributes to tumor progression and dedifferentiation, highlighting nuclear HER2/ErbB3 complexes as potential prognostic biomarkers and therapeutic targets in ccRCC.

The lymphatic system, hematogenous system, and implantation represent the major metastatic routes of gynecologic malignancies, among which lymphatic dissemination is the most prevalent and closely linked to patient prognosis. While vascular metastasis has been extensively studied, with well-established mechanisms such as tumor-induced angiogenesis, immune mimicry, and stromal remodeling, research on lymphatic metastasis remains relatively limited. This gap is largely attributable to the poor visibility of lymphatic vessels, the delayed identification of specific biomarkers, and the technical and economic challenges of isolating primary lymphatic endothelial cells. Consequently, the depth of research on lymphatic metastasis lags far behind than that of hematogenous metastasis, especially the targeted investigations into gynecologic tumor-associated lymphatic vessels (TALVs) are still at an early stage. This manuscript first reviews the current progress in mechanistic studies of lymphatic metastasis in gynecologic malignancies, then highlights the mainstream clinical lymphatic imaging techniques and experimental models in basic research, and finally discusses feasible gene detection approaches for further reference.

Malformin A1 (MA1), a fungal-derived cyclic pentapeptide, has been reported to exhibit anti-cancer activity. 5-fluorouracil (5-FU) is a widely used chemotherapeutic agent that inhibits DNA and RNA synthesis and suppresses colorectal cancer (CRC) cell growth. This study aimed to investigate whether MA1 enhances the anticancer effects of 5-FU in CRC cells.

The effects of MA1 and 5-FU on CRC cells were evaluated using the WST-1 cell viability assay, DNA fragmentation analysis, flow cytometry, and western blotting.

MA1 treatment demonstrated greater cytotoxic activity in CRC cells compared to 5-FU alone. Combined MA1 treatment enhanced 5-FU-induced apoptosis through activation of PARP, caspase-3, and caspase-9, along with decreased expression of anti-apoptotic proteins Mcl-1 and Survivin, compared with the non-combined treated control. In addition, combined MA1 treatment potentiated 5-FU-induced cell cycle arrest at the sub-G₁ phase by increasing p57 protein levels and reducing cyclin D1, CDK6, and Cdc25C protein expression relative to the non-combined treated control. Furthermore, combined MA1 treatment augmented 5-FU-induced inhibition of umbilical vein endothelial cell invasion, tube formation, and the expression of vascular endothelial growth factor (VEGF)-A and -D. The phosphorylation levels of p38 and c-Jun NH2-terminal kinase (JNK) were further upregulated by combined MA1 treatment in CRC cells compared to the non-combined treated control.

MA1 enhances 5-FU-induced apoptosis, cell cycle arrest, and anti-angiogenic effects in CRC cells through activation of the p38 and JNK signaling pathways. These findings suggest that the combination of MA1 and 5-FU may represent a potential strategy to overcome resistance to 5-FU in CRC cells.

Neurofibromatosis type 1 (NF1) is characterized by the development of neurofibromas, including cutaneous neurofibromas and plexiform neurofibromas (PNFs). Despite more than a century of clinical recognition, the terminology used to describe these tumors remains inconsistent across disciplines, particularly in pathology, radiology, and clinical practice. This lack of standardized nomenclature complicates communication, diagnostic assessment, risk stratification, and therapeutic decision-making. In this multidisciplinary consensus paper, experts from the German NF Working Group sought to harmonize current terminology for NF1-associated neurofibromas, with particular emphasis on PNF, and to relate this terminology to diagnostic procedures, clinical course, and treatment considerations. A new structured terminology of NF integrating anatomic and histological descriptions is proposed. Using a modified Delphi process, the group developed consensus statements addressing the definition and classification of neurofibromas and their relevance for imaging, pathology, surgery, biopsy, and medical treatment. A unified terminology is especially important in the era of targeted therapy, as MEK inhibitors have emerged as a promising treatment option for selected patients with NF1-associated PNF. Establishing a shared conceptual framework may improve interdisciplinary communication, support more consistent clinical decision-making, and provide a stronger basis for future recommendations on the use of MEK inhibitors in NF1.

Poor prognosis of brain tumors is partly related to the blood brain barrier (BBB) to hydrophilic anticancer drugs. Early studies demonstrated that intracranial injection of vital dyes bypassed BBB in cats. We investigated if intraventricular infusion of gemcitabine can circumvent the blood-brain barrier and achieve therapeutically relevant drug concentrations within the brain and cerebrospinal fluid.

Brain diffusion of the vital hydrophilic Bleu Patente dye was studied after intracranial or intravenous injection in guinea pig, or after a 24 h protracted intraventricular infusion in sheep. Gemcitabine, a hydrophilic anticancer drug, was quantified by high-performance liquid chromatography. Viability of human glioblastoma cells was studied in vitro. Cells were maintained in drug-free fresh culture medium for 72 h after drug exposure before an assay with Crystal Violet. Tolerance of a single 24 h intraventricular infusion of gemcitabine was evaluated in sheep.

Bleu Patente diffused into brain of guinea pigs after an intracranial injection, whereas brain remained unstained after an intravenous administration. After a 24 h intraventricular infusion, dye penetrated deeply into the cerebral cortex of sheep. Brain concentration of gemcitabine was higher following intracranial injection than after intravenous administration in guinea pigs. At the end of a 24 h intraventricular infusion of 20 mg gemcitabine in sheep, mean concentrations reached 1,415 microg/l in cerebrospinal fluid and 850 microg/kg in brain. These concentrations exceeded the IC₉₀ values of gemcitabine for A172, U87-MG, and U118-MG human glioblastoma cell lines. Tolerance of a single 24 h intraventricular infusion of 20 mg gemcitabine was good in sheep.

We hypothesize that intraventricular injections allow the hydrophilic drugs to circumvent BBB by using the glymphatic system. Given high concentrations in the cerebrospinal fluid and brain, and given its good tolerability, we propose to study protracted intraventricular infusion of gemcitabine in patients with refractory primary, secondary brain tumors, and meningeal metastasis.

Dedifferentiated liposarcoma (DDL) is defined by amplification of chromosome 12q13-15 but exhibits substantial morphologic heterogeneity, including variable stromal composition. This study aimed to determine whether prominent stromal patterns in DDL are associated with distinct immunophenotypic and genomic profiles.

Nineteen surgically resected DDLs were evaluated for histologic features, immunophenotype, and targeted genomic alterations using next-generation sequencing. Associations between stromal pattern, immunohistochemistry, copy number alterations, and clinical outcome were analyzed.

All cases demonstrated MDM2 amplification and strong nuclear MDM2 expression, with frequent co-amplification of CDK4. Beyond canonical 12q alterations, recurrent amplifications were identified, including 1q23 (DDR2), 5p15 (TERT), and 12q13 (STAT6). Notably, DDR2 amplification was significantly enriched in collagenous-dominant DDLs compared with myxoid-dominant tumors. Stromal pattern correlated with immunophenotype, with collagenous-dominant tumors showing frequent SMA expression and absence of CD34, whereas myxoid-dominant tumors more frequently expressed CD34. High mitotic activity and mFNCLCC grade 3, but not stromal pattern, were associated with adverse outcome.

Prominent stromal patterns in DDL reflect biologically meaningful subsets associated with distinct immunophenotypic features and secondary genomic alterations. In particular, enrichment of DDR2 amplification in collagenous-dominant DDL suggests a potential link between collagen-associated signaling pathways and stromal morphogenesis in this tumor.

Understanding why some leukemia cells undergo apoptosis upon venetoclax (VEN) treatment while others remain refractory is essential for improving therapeutic outcomes. Here, we integrate Raman microscopy, FT-IR imaging, and chemometrics to explore treatment-associated spectroscopic patterns linked to differential VEN response in Philadelphia-positive B-cell acute lymphoblastic leukemia (Ph+ B-ALL). Using two BCR-ABL1-positive cell lines with intrinsic differences in VEN sensitivity (BV-173, sensitive; SD-1, resistant), we combined classical biological readouts of apoptosis with multimodal vibrational profiling to characterize global biochemical changes induced by VEN. Sensitive BV-173 cells displayed spectroscopic changes consistent with apoptotic progression, reflected in coordinated alterations in nucleic acids, proteins, and lipids. In contrast, resistant SD-1 cells exhibited a distinct treatment-associated biochemical response profile consistent with nonapoptotic adaptation. Spectroscopic fingerprints enabled differentiation between apoptotic and nonapoptotic response patterns in the cell-line models studied. Our findings demonstrate that vibrational spectroscopy, integrated with chemometrics, may provide a complementary analytical framework for exploratory characterization of treatment-associated biochemical phenotypes in leukemia.

Sensitive and specific detection of low-frequency mutations in circulating tumor DNA (ctDNA) remains a major challenge because mutant alleles typically constitute less than 1% of the total cell-free DNA in plasma. Herein, we present a blocker primer-assisted loop-mediated isothermal amplification (LAMP) assay coupled with Pyrococcus furiosus Argonaute (PfAgo) for detection of EGFR mutations associated with nonsmall cell lung cancer (NSCLC). A blocker primer was incorporated into the LAMP reaction to selectively suppress wild-type (WT) amplification and enrich the mutant-derived amplicons. The mutant amplicons were subsequently recognized and cleaved by PfAgo. The resulting cleavage fragments acted as secondary guides to trigger cleavage of fluorogenic probes, enabling cascade signal amplification. The assay detected the EGFR L858R, T790 M and 19del at mutant allele frequencies as low as 0.05% in a strong WT background (1 × 106 copies/μL total DNA) and reliably detected target mutations in lung cancer cell lines. In clinical plasma samples, the assay detected EGFR L858R with 84.62% sensitivity and 100% specificity relative to next-generation sequencing (NGS). These results demonstrate that the blocker primer-assisted LAMP coupled with PfAgo assay is a specific and sensitive approach for ctDNA mutation analysis and shows promise for liquid biopsy applications.