Regarding "druggable markers," DLL3 was expressed in 66% of tumors and PD-L1 in 17.4%. Detailed analyses of different prognostic and predictive markers are needed to better understand EP-SCNC biology and create more personalized therapy to improve patient prognosis.

11 months ago

Journal • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • DLL3 (Delta Like Canonical Notch Ligand 3) • YAP1 (Yes associated protein 1) • NCAM1 (Neural cell adhesion molecule 1) • POU2F3 (POU Class 2 Homeobox 3) • SYP (Synaptophysin) • ASCL1 (Achaete-Scute Family BHLH Transcription Factor 1) • NEUROD1 (Neuronal Differentiation 1)

TP53 mutation • BRCA2 mutation • RB1 expression • BRCA2 mutation + TP53 mutation • YAP1 overexpression

1year

P16INK4A drives RB1 degradation by UTP14A-catalyzed K810 ubiquitination. (PubMed, iScience)

Our findings indicate that there is a negative feedback loop between P16INK4A and RB1 expression and that disruption of this loop may partially rescue the biological outcomes of P16INK4A loss. We also revealed a hitherto unknown function for P16 INK4A in regulating proteome-scale ubiquitination by inhibiting cell proliferation, which may be useful for the development of anticancer drugs.

1 year ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CDK4 (Cyclin-dependent kinase 4)

RB1 expression • CDKN2A expression

1year

Application of the 5th WHO Guidelines for the Diagnosis of Lung Carcinoma in Small Lung Biopsies in a Tertiary Care Center: Is Insecurity of Pathologists for the Accurate Diagnosis Justified? (PubMed, Diagnostics (Basel))

Our study confirms the diagnostic certainty achieved by the suggestions of the WHO classification and justifies the potential insecurity in the absence of adequate communication with the treating clinician.

1 year ago

Journal • Biopsy

RB1 (RB Transcriptional Corepressor 1) • TP63 (Tumor protein 63)

RB1 expression

1year

RB1 Mutations Induce Smoking-Related Bladder Cancer by Modulating the Cytochrome P450 Pathway. (PubMed, Environ Toxicol)

In addition, we also observed that the component of immunological cells was regulated by RB1 mutations through the stronger cell-to-cell interactions between epithelial scissor+ cells and immune cells in smokers. This study highlighted that RB1 mutations could drive smoking-related bladder tumorigenesis through inhibiting cytochrome P450 pathway and regulating tumor immune microenvironment.

1 year ago

Journal • Tumor mutational burden

TMB (Tumor Mutational Burden) • RB1 (RB Transcriptional Corepressor 1) • AKR1C2 (Aldo-Keto Reductase Family 1 Member C2) • UGT1A6 (UDP Glucuronosyltransferase Family 1 Member A6)

RB1 mutation • RB1 expression

over1year

Uterine Leiomyosarcoma Associated With Perivascular Epithelioid Cell Tumor: A Phenomenon of Differentiation/Dedifferentiation and Evidence Suggesting Cell-of-Origin. (PubMed, Am J Surg Pathol)

We hypothesize that LMSs containing smooth muscle progenitor cells may give rise to divergent, lineage-specific PEComatous lesions through differentiation or dedifferentiation. While we do not dispute the recognition of PEComas as a distinct entity, we advocate the hypothesis that modified smooth muscle cells represent the origin of a subset of PEComas, and our case series provides evidence to suggest this theory.

over 1 year ago

Journal

TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • ATRX (ATRX Chromatin Remodeler) • FH (Fumarate Hydratase) • GPNMB (Glycoprotein Nmb) • CTSK (Cathepsin K)

TP53 mutation • RB1 expression • TP53 expression • TP53 R196*

over1year

Generation and characterization of three CRISPR/Cas9 edited RB1 null hiPSC lines for retinoblastoma disease modelling. (PubMed, Stem Cell Res)

Two of the mutant lines are compound heterozygous, with different in-del mutations in each of their alleles, while the third mutant line is homozygous, with identical edits in both alleles. All lines maintained their stemness, pluripotency, formed embryoid bodies with cell types of all three lineages, displayed a normal karyotype and lost RB1 expression.

over 1 year ago

Journal

RB1 (RB Transcriptional Corepressor 1)

RB1 expression

almost2years

Atypical spindle cell/pleomorphic lipomatous tumor with sarcomatous transformation: clinicopathologic and molecular analysis of four cases. (PubMed, Mod Pathol)

Limited clinical follow-up showed no recurrence or metastasis after 1-13 months (median 4.5 months) post-surgical excision. Altogether, our data support that ASPLT can rarely develop sarcomatous transformation and offers insights into the molecular mechanisms underlying this event.

almost 2 years ago

Journal

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • ATRX (ATRX Chromatin Remodeler)

RB1 deletion • RB1 expression

almost2years

CD63+ cancer-associated fibroblasts confer CDK4/6 inhibitor resistance to breast cancer cells by exosomal miR-20. (PubMed, Cancer Lett)

Most importantly, we designed and synthesized cRGD-miR-20 sponge nanoparticles and found that they can enhance the therapeutic effect of CDK4/6i in breast cancer. In summary, our findings reveal that CD63+ CAFs can promote CDK4/6i resistance via exosomal miR-20, which induces the downregulation of RB1 in breast cancer cells, and suggest that CD63+ CAFs may be a novel therapeutic target to enhance CDK4/6i sensitivity.

almost 2 years ago

Journal

RB1 (RB Transcriptional Corepressor 1) • CDK6 (Cyclin-dependent kinase 6)

HR positive • RB1 expression

almost2years

Loss of Function of the Retinoblastoma Gene Affects Gap Junctional Intercellular Communication and Cell Fate in Osteoblasts. (PubMed, Biology (Basel))

Our observations suggest that increased PPAR-ɣ that happens with Rb1 loss only affects osteoblast-adipocyte-specific gene expression but does not completely reverse Cx43 gene expression or GJIC. Therefore, these effects may represent independent events triggered by Rb1loss and/or the differentiation process.

almost 2 years ago

Journal

RB1 (RB Transcriptional Corepressor 1) • CDH2 (Cadherin 2) • GJA1 (Gap Junction Protein Alpha 1) • CDH11 (Cadherin 11) • RUNX2 (RUNX Family Transcription Factor 2)

RB1 expression • GJA1 expression

2years

Network pharmacology-based research on the effect of Scutellaria baicalensis on osteosarcoma and the underlying mechanism. (PubMed, Medicine (Baltimore))

Scutellaria baicalensis acted on osteosarcoma by regulating a signaling network formed by hub targets connecting multiple signaling pathways. Scutellaria baicalensis appears to have the potential to serve as a therapeutic drug for osteosarcoma and to prolong the survival of OS patients.

2 years ago

Journal

ER (Estrogen receptor) • RB1 (RB Transcriptional Corepressor 1) • IL6 (Interleukin 6) • MAPK1 (Mitogen-activated protein kinase 1) • PPARG (Peroxisome Proliferator Activated Receptor Gamma) • CDK1 (Cyclin-dependent kinase 1) • IL1B (Interleukin 1, beta) • RXRA (Retinoid X Receptor Alpha) • MAPK14 (Mitogen-Activated Protein Kinase 14) • RELA (RELA Proto-Oncogene)

RB1 expression • IL6 expression

2years

Fibroepithelial Stromal Polyp of the Vulvovaginal Region as Part of the RB1 Family of Tumors: Friend or Foe? (PubMed, Int J Gynecol Pathol)

Based on our findings, we hypothesize that FSPs are part of a spectrum of genetically related lesions, namely the 13q/RB1 family of tumors (which includes pleomorphic fibromas and spindle cell/pleomorphic lipomas). Due to the clinical, morphologic, and molecular overlap, we suggest that FSPs are pleomorphic fibromas occurring in the specialized stroma of the genital region.

2 years ago

Journal • Stroma

RB1 (RB Transcriptional Corepressor 1)

RB1 deletion • RB1 expression • RB deletion

2years

Depleted Hexokinase1 and lack of AMPKα activation favor OXPHOS-dependent energetics in Retinoblastoma tumors. (PubMed, Transl Res)

AMPKα activation by AICAR also enhanced the tumoricidal effects of the chemotherapeutic drug topotecan in vivo. Therefore, enhancing HK1 or AMPKα activity can reprogram cancer metabolism and sensitize retinoblastoma tumors to lower doses of existing treatments, a potential therapeutic modality for retinoblastoma.

2 years ago

Journal

STK11 (Serine/threonine kinase 11) • RB1 (RB Transcriptional Corepressor 1) • HK1 (Hexokinase 1)

RB1 expression

topotecan