RB1 expression

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.

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.

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.

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.

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.

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.

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.

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.

No specific molecular genetics changes have been identified so far. Familiarity with its clinicopathological features helps the distinction from its morphologic mimics.

We have reported a case of RB-associated bladder leiomyosarcoma that was successfully treated during and after pregnancy.

Our results highlight the correlations between the p53/Rb1 immunostainings and the histopathological diagnosis of high-grade GI-NENs. NECs and NEC components in MiNENs showed a p53 mutational status (0% or 21-100%) and predominantly negative Rb1 expression. NETs G3 showed a p53 wild-type status (1-20%) and retained Rb1 expression. These findings suggest that the differential diagnosis of high-grade GI-NENs may benefit from p53/Rb1 immunohistochemical tests in everyday practice.

The reduction of miR-132 and RB1 expression confirmed the tumor-suppressive role of both genes in breast cancer. Considering that RB1 is one of the miR-132 targets, further studies are required to discover any miRNA-mediated upregulation role for miR-132. Our finding discovered a small linear association between miR-132 and RB1, which can be concluded towards their independent function in breast cancer pathogenesis.

MiR-4529-3p promotes RB progression by inhibiting RB1 and activating the ERK pathway. This evidence suggests that the miR-4529-3p/RB1 regulatory axis may be a prospective target for RB treatment in clinical settings.

Nuclear p85β represses RB1 expression by stabilizing histone methyltransferase EZH1/EZH2 proteins. Last, the FAK inhibitor defactinib significantly suppresses the tumor growth of ccRCC with high p85β Y464 levels.

This finding revealed the dispensable role of RB in regulating MYCN-amplified NB's cell cycle. The described genetic interaction between MYCN and RB1 provides the rationale for using cyclin/CDK complexes inhibitors in NBs carrying MYCN amplification and relatively high levels of RB1 expression.

We identify a new small molecule, AP-3-84, with therapeutic potential in AML by its binding to the LxCxE pocket of Rb1 triggering mitochondria-mediated cell apoptosis.

A small molecule OC2 inhibitor blocked enzalutamide-induced lineage plasticity in vitro. These findings indicate that activation of OC2 in CRPC occurs in response to RB1 inactivation, and that biomarkers of RB1 activity may be useful for stratifying patients refractory to hormone therapy where OC2 is targeted pharmacologically.

SCLC cells and xenograft tumors with RB1 protein expression were sensitive to growth inhibition by the CDK4/6 inhibitor palbociclib, and this inhibition was shown to be dependent on RB1 expression by CRISPR knockout. Finally, we identified a transcriptomics-based RB1 loss-of-function signature that discriminates between SCLC cells with or without RB1 protein expression and validated it in the patient who was responsive to abemaciclib, suggesting its potential use to predict CDK4/6 inhibitor response in SCLC patients. Our study demonstrates that RB1 protein is an actionable target in a subgroup of SCLC, a cancer that exhibits no currently targetable mutations.

In addition, regulatory T cells (Tregs) were detected as a negatively correlated type of immune cell to mutation of RB1, whereas fluorescence costaining showed that Foxp3 expression of Tregs infiltration was negatively related to the expression of RB1. Mutation of RB1 can be identified as an independent prognostic predictor of BCa, and it may suppress the infiltration of Tregs in BCa tissues, increasing the incidence of tumor immune escape.

Collectively, our results unveil a novel molecular mechanism by which VNN1 promotes AKI-CKD transition via inducing senescence of renal tubular cells by activating RB1 expression and phosphorylation after severe renal injury. The present study proposes a new strategy for designing therapies wherein VNN1 can be targeted to obstruct the AKI-CKD transition.

One hundred and thirty-one and 490 miRNA binding sites were observed for TP53 and RB1, respectively, most of which were in seedless regions. These findings suggest that up-regulation of miRNA expression can directly repress TP53 and RB1 expression by their binding sites in the non-canonical seedless regions.

SOX2 diffuse expression was observed in 92% of the MCC cases and almost never observed in non-neuroendocrine skin epithelial neoplasms (2%, p < 0.0001, LHR +  = 59). Furthermore, SOX2 diffuse staining was more frequently observed in MCCs than in extra-cutaneous NECs (30%, p < 0.001, LHR +  = 3.1).These results confirm RB1 as a robust predictor of MCC viral status and further suggest SOX2 to be a relevant diagnostic marker of MCC.

The combination of downregulation of RB1 and overexpression of SSTR5-AS1 is a strong predictor of shorter time to castration-resistant prostate cancer in the Indonesian population. Additionally, patients with International Society of Urological Pathology (ISUP) score >4 did not demonstrate this predictive value on time to castration-resistant prostate cancer.

P1, N=15, Active, not recruiting, Children's Oncology Group | Trial completion date: Dec 2021 --> Jun 2025 | Trial primary completion date: Dec 2021 --> Jun 2021

Our results indicate that miR-17 expression impairs normal osteogenesis by downregulating RB1 expression and significantly inhibiting the function of BMP9.

The PALLET phase II randomized neoadjuvant trial of letrozole (LET) ± palbociclib (PALBO) in postmenopausal ER+HER2- primary breast cancer showed that suppression of proliferation as measured by Ki67 was significantly greater with addition of PALBO to LET but did not result in all patients achieving complete cell-cycle arrest, indicating intrinsic resistance in some patients. We observe, confirming previous studies, an association of CDK4/6 inhibitor resistance, high expression of CCNE1 and genes related to interferon gamma signalling. We show that there is an overlap between resistance mechanisms and TP53 mutations. However, ER+HER2- patients with TP53 mutations may still benefit from PALBO adding to suppression of proliferation compared to LET-only treatment.

The mRNA expression of SLC2A1 was significantly higher in breast cancer. The overall survival of breast cancer patients wasn't significantly correlated with GLUT1-4 expression. The mRNA expression of SLC2A1 and RB1 is significantly correlated according to the analysis conducted in LinkedOmics. It provides reference for future possible individualized treatment of TNBC using GLUT1 inhibitors, especially in patients with higher mRNA expression of RB1. Further study analyzing the roles of these two genes in the regulation pathways is needed.

p53 and Rb1 are powerful markers in the distinction of NET G3 from NEC. Rarely, carcinomas from non-digestive, non-pulmonary organs with neuroendocrine features may present as NET G3.

P1, N=15, Active, not recruiting, Children's Oncology Group | Trial completion date: Jun 2021 --> Dec 2021 | Trial primary completion date: Jun 2021 --> Dec 2021

Furthermore, NEC-GYN exhibited a highly immunosuppressive state, intact RB1 expression, and was uniquely enriched with the YAP1 molecular subtype. Our study identifies several potential therapeutic targets and suggests an urgent need to reevaluate the treatment options for NEC-GYN.

RB1 overexpression enhanced 5-FU chemosensitivity in GC cells by regulating cell autophagy via SDF-1/CXCR4 pathway. RB1 might serve as a promising therapeutic target of GC.

P1, N=15, Active, not recruiting, Children's Oncology Group | Trial completion date: Mar 2021 --> Jun 2021 | Trial primary completion date: Mar 2021 --> Jun 2021

Although the combination of palbociclib + fixed-dose vemurafenib did not allow an increased palbociclib dosage above 25mg, a significant clinical benefit was achieved in pretreated melanoma patients. An association between the transcriptomic data and clinical response was highlighted.

P2; CTC count seems to be a promising modality in monitoring palbociclib response. Moreover, CTC count at the time of progression could predict clinical outcome post-palbociclib. RB1 expression analysis on CTCs is feasible and may provide additional prognostic information. Results should be interpreted with caution given the small studied sample size.

P1, N=15, Active, not recruiting, Children's Oncology Group | Recruiting --> Active, not recruiting

Molecular docking and other studies confirmed that curcumin could bind to and upregulate the expression of TET2 and TET3 with hydrogen bonds and arene-H bonds, suggesting that demethylation of RB1 was attributed to reactivation of the demethylation enzymes TET2 and TET3 after curcumin treatment. Thus, our findings reveal a promising therapeutic strategy for gastric cancer prevention and treatment through RB1 demethylation and reactivation.