MUC4 expression

DNA methylation analysis further showed that YAP1::KMT2A-rearranged sarcomas formed a distinct cluster, which was clearly separate from both conventional SEF and low-grade fibromyxoid sarcoma (LGFMS). These results suggest that YAP1::KMT2A-rearranged sarcomas likely represent a unique sarcoma subtype with propensity for aggressive behavior.

DICER1MUT and DICER1WT tumors showed different mRNA expression profiles. The FOXL2 mutation is less common in these tumors and is mutually exclusive with the DICER1 mutation.

The study's results indicate that MUC1 & 4 individually are crucial for monitoring OSCC and OPMD pathogenesis as the former gives an idea of highly undifferentiated grades while the latter indicated more differentiated tumors and perhaps a better prognosis. Therefore, the two can be useful tumor markers for determining the severity and eliminating it in its early phases.

Treatment of Capan-1 and AsPC-1 cells with BAs or with human serum obtained from PDAC + OJ patients enhanced the expression of MUC17, as well as the proliferative potential of the cells, whereas knockdown of MUC17 alone or in combination with MUC4 decreased BAs-induced carcinogenic processes. Our results demonstrated that MUC17 has a central role in bile-induced PC progression, and in addition to MUC4, this isoform also can be used as a novel prognostic biomarker.

CK7 + tumors showed intriguingly common (31.6%) BRAF V600E mutations corelating with poor prognosis, compared to the frequency described in the literature and databases. Further research on larger cohorts with a non-colorectal immunophenotype and high MUC4 expression is needed.

We unveiled region-specific mucin RNA isoform panels capturing the heterogeneity of the IBD patient population and showing great potential to indicate barrier function in IBD patients.

SEF is typically identified via genetic testing and recognition of the EWSR1-CREB3L1 gene fusion as well as MUC4 expression via immunohistochemistry. DNA methylation profiling, which has traditionally been used in brain tumors, can also efficiently identify this tumor, and we recommend expanding the use of this technology for difficult to classify pediatric sarcomas.

This series further solidifies the notion that FET::CREB fusions are not limited to the triad of angiomatoid fibrous histiocytoma, clear cell sarcoma, and malignant gastrointestinal neuroectodermal tumor, but characterize an emerging family of potentially aggressive neoplasms occurring at both intra- and extra-abdominal sites. These tumors underscore the promiscuity of the FET::CREB fusions and highlight the pivotal role of phenotype-oriented classification of these neoplasms that share the same genotype, still featuring significant biological and behavioral distinctness.

A total of 83 differential metabolites associated with the amelioration of VB6 were identified, which were primarily enriched in glycerophospholipid metabolism, caffeine metabolism, and glutathione metabolism pathway. Collectively, VB6 may improve the growth performance and intestinal barrier function of heat-stressed broilers by regulating the ileal microbiota and metabolic homeostasis.

Notably, similar to CAFs, immunosuppressive tumor-associated macrophage (TAM) subtypes underwent glycolipid metabolism reprogramming via PPARgamma regulation, promoting tumor metastasis. These findings shed light on the mechanisms driving the aggressiveness of HGSC, offering crucial insights for the development of novel therapeutic targets against this formidable cancer.

Differential expression of MUC-4 in pancreatic tumor tissues can help to differentiate PDAC from benign conditions.

Thus, C. butyricum B14 administration helps regulate the balance of the intestinal microecology. It can suppress immune pathways and enhance barrier-protective proteins.

On follow-up, 1 patient developed multiple spinal bone metastases 5 months after the surgery while the other two patients were free of disease 9 and 120 months after diagnosis, respectively. Our findings demonstrate that intra-abdominal epithelioid neoplasms with EWSR1::CREB fusions may rarely occur primarily in the kidney and should be included in the differential diagnosis of primary renal epithelioid mesenchymal neoplasms.

We have demonstrated that TNF induces trastuzumab resistance through mucin 4 (MUC4) upregulation and it is an independent biomarker of poor response to therapy in HER2+ breast cancer...TNF blockade was achieved with etanercept (E), which blocks the soluble (sTNF) and transmembrane isoform of TNF, or with the dominant negative protein INB03 (DN) which neutralizes only sTNF...MUC4 is associated with poorly-infiltrated TNBC, and sTNF blockade downregulates its expression decreasing MTS when combined with anti-PD-1. We propose the TNF as a new target for the treatment of TNBC, and MUC4 as a predictive biomarker to guide a combined treatment of TNF blockers with immunotherapy.

Conclusion In conclusion, this study adds to our understanding of soft tissue sarcomas by emphasizing the crucial role of MUC4 in certain sarcoma subtypes while acknowledging the complex variety of the sarcoma landscape. Further research is needed to understand the molecular mechanism that governs marker expression patterns, as well as the therapeutic implications.

The SBA immunophenotype correlated with tumor location, biological behavior, and genomic alterations. Our results suggest that the molecular pathway involved in carcinogenesis of gastric-type SBA differs from that of intestinal-type SBA.

We identified a GALNT family gene, GALNT14, that was highly expressed in osteosarcoma. This gene was closely associated with metastasis, progression, cuproptosis-related genes, and chemosensitivity of osteosarcoma, and showed correlation with poor overall survival and disease-free survival in osteosarcoma.

The net MM/GBSA energy value of the ZINC585267910-MUC4 complex estimated was -46.84 kcal/mol and that of the ZINC585268691-BIRC3 complex was -44.84 kcal/mol. In a nutshell, the compounds might be investigated further as an inhibitor of the said proteins to stop the progress of GC induced by H. pylori.Communicated by Ramaswamy H. Sarma.

The recognition of massive degeneration and hyalinization as unusual features of LGFMS might be helpful to differentiate it from CEH and other benign spindle-cell tumors.

In preclinical models of de novo trastuzumab-resistant tumors, combination of a sTNF blocking agent INB03, (DN), with T-DXd decreases tumor growth compared to T-DXd alone...Methods Nude mice bearing HER2+MUC4+ JIMT-1 tumor, primary resistant to trastuzumab, pertuzumab and lapatinib, were treated with IgG 5 mg/kg, T-DXd 5 mg/kg (T-DXd 5), 2.5 mg/kg (T-DXd 2.5) or 1.25 mg/kg (T-DXd 1.25), DN 10 mg/kg or the combined therapies...Combination of DN with T-DXd in MUC4 expressing HER2+ BC improves response to T-DXd alone by increasing T-DXd internalization and improving anti-tumor innate immune responses in the TME without increasing toxicity. The results suggest this combination should be investigated in clinical trials in patients who have MUC4 expressing tumors when T-DXd is started or become resistant to T-DXd therapy.

Identification of recurrent gene abnormalities (RGA) B-acute lymphoblastic leukemia (B-ALL) cases using multiplex-reverse transcriptase polymerase chain reaction. Identification and characterization of Philadelphia (Ph)-like ALL cases using nCounter NanoString gene expression profiling and fluorescence in situ hybridization. Furthermore, Ph-like ALL cases were characterized according to CRLF2 expression and kinase-activating genomic alterations. Minimal residual disease of Ph-like ALL cases were quantified using flow cytometry-minimal residual disease assay. A surrogate molecular approach was established to detect Ph-like ALL cases from low- and middle-income countries.

Further research is needed to explain differences in pathogenesis compared with other pNENs. In particular, multi-omics data such as RNASeq, methylation and whole genome sequencing could be informative.

The histological expression of CA 19-9 may predict prognosis. MUC4, MSLN, ANXA10, and GPC-1 are selectively expressed by neoplastic tissue and may represent a potential histological biomarker of disease.

Using a mouse model, we have delineated metaplastic pit cells as a precancerous cell type whose expansion requires Hp-driven inflammation. In humans, metaplastic pit cells show enhanced proliferation as well as enrichment in precancer and early cancer tissues, highlighting an early step in the gastric metaplasia to cancer cascade.

A loss of the stimulatory effects of HM on COX-2, PGE2 and IL-6 production and secretion was observed in TAK242 and NS-398-pre-treated AGS cells, confirming the role of TLR4 signaling and COX-2 generated in the HM gastroprotective effects. In conclusion, our results showed that HM enhances TLR4/COX-2-mediated secretion of gastroprotective markers PGE2 and IL-6, and upregulates mucin 4 gene expression in the human gastric epithelial cell line AGS, which may contribute to the promising beneficial gastroprotective effect of HM for human gastric prevention and treatment.

Strong and diffuse MUC4 expression is highly specific in this histologic context. Detection of an FUS or EWSR1 rearrangement can confirm the diagnosis.

No responses were seen to trabectedin. The metastatic course of F and S may be indolent. When systemic therapy is needed, gemcitabine-based regimen and pazopanib currently seem to be most active. Responses were seen also to ifosfamide and oral cyclophosphamide.

Lastly, we performed a correlation analysis and found that the combination of EEF2, GAPDH, and PGK1 represents the best combination with a very high correlation in Ph-like ALL cases. This is the first report that shows EEF2, GAPDH, and PGK1 are the best HKG genes and can be used in the diagnostic panel of Ph-like ALL cases using qPCR at baseline diagnosis.

These observations highlight that lncRNA BBOX1-AS1 is an essential NPC progression promoter and suggest that the lncRNA BBOX1-AS1/miR-204-5p/MUC4 axis is a potential therapeutic target in NPC.

Mucinous and glandular/luminal cells were identified in significantly more mammary hidradenomas than non-mammary lesions. The findings provide insight into the pathogenesis of MAML2-rearranged neoplasms of the breast, underscore the overlapping genetic features of MEC and hidradenoma, and highlight similarities to their extramammary counterparts.

This study proved that MUC13 is an important molecule that regulates the O-glycan process and then affects the progress of esophageal cancer. MUC13 may be a novel therapeutic target for patients with esophageal cancer.

Although SCsg failed to demonstrate a complete lactational-like differentiation, lactoferrin showed a distinctive expression pattern in SCsg compared to other tumour types, which makes it a good marker to help in its differential diagnosis.

In vivo, capivasertib (an AKT inhibitor) increased GEM sensitivity in GR cells. In GR CCA, high MUC4 expression promotes sustained EGFR/HER2 signaling and AKT activation. The combination of AKT inhibitors with GEM or afatinib might overcome GEM resistance.

This novel subset of female adnexal neoplasms should be included in the differential diagnosis of any epithelioid neoplasm involving female adnexa. Their aberrant immunophenotype can be misleading, underlining a wide spectrum of differential diagnosis.

In conclusion, MUC4 is a specific, albeit insensitive, marker for these high-risk subtypes of B-ALL. We propose that MUC4 IHC may be employed diagnostically to rapidly identify these B-ALL subtypes particularly in resource limited settings or when an aspirate sample is not available for ancillary genetic studies.

Analysis of the expression profile of MUC4 and the aberrant expression of this gene in OSCC suggests that it may serve as a useful diagnostic marker. Therefore, it is possible to draw the conclusion that MUC4 plays a very significant part in the pathogenesis of OSCC and also acts as a marker that may be taken into consideration for the accurate diagnosis of OED and OSCC.

No abstract available

We have demonstrated that the proinflammatory cytokine TNFα induces trastuzumab resistance through Mucin4 (MUC4) upregulation and it is an independent biomarker of poor response to therapy in HER2+ breast cancer...TNFα blockade was achieved using etanercept (E), which blocks the soluble (sTNFα) and transmembrane isoforms of TNFα, or dominant negative protein INB03 (DN) which only neutralizes sTNFα...MUC4 is an independent biomarker of poor overall survival, it is associated with an increased risk of metastasis and immune desert tumors. We propose TNFα as a new target for the treatment of TNBC, and MUC4 as a predictive marker to guide a combined treatment of TNFα blockers with chemotherapy or immunotherapy.

Background: RXC004 is a potent and selective inhibitor of the Wnt pathway regulator Porcupine, and is currently being investigated in phase 2 studies in patients with advanced cancers, including Biliary Tract Cancers (BTCs) +/- Pembrolizumab (NCT04907851 and NCT04907539). These data demonstrate that (1) RXC004 is efficacious in pre-clinical PDX models of BTC, (2) RXC004 induces multiple PD effects in BTC models at the level of gene expression, cell proliferation and cell differentiation, and (3) PDX models of BTC can be clustered based on baseline transcriptomic profiles of Wnt signalling genes and predict RXC004 sensitivity.

Here, we study whether sTNFα blockade with INB03 (DN) plays a role in regulation of innate immunity to enhance T-DXd antitumor effects in a multiple HER2-targeted therapy-resistant model. Nude mice bearing HER2+MUC4+ JIMT-1 tumor, primary resistant to trastuzumab, pertuzumab and lapatinib, were treated with IgG 5 mg/kg, T-DXd 5 mg/kg (T-DXd 5), 2.5 mg/kg (T-DXd 2.5) or 1.25 mg/kg (T-DXd 1.25), DN 10 mg/kg or the combined therapies...Adding DN allows to lower T-DXd doses to induce a reinforced antitumor innate immune response, reduced tumor cell mitosis and achieve similar tumor inhibition. Since sTNFα and MUC4 expression proved to be important variables in the response to T-DXd, neutralizing this cytokine may open new therapeutic strategies to treat patients with MUC4 expressing tumors or have progression on T-DXd therapy.