CDKN2A overexpression

Our data strongly support investigation of the chemotherapy-free palbociclib and venetoclax combination as an innovative treatment strategy for post-ibrutinib MCL patients without RB1 deletion.

To conclude, the mean viral load in HPVDNA+/p16+ OPSCC was higher than in HPVDNA+/p16- OPSCC, but there was no statistically significant difference in viral load depending on OPSCC subsite or on clinical outcome.

Our findings demonstrate that CDKN2A downregulation in glioblastoma cells is associated with decreased cell viability, enhanced drug resistance, increased self-renewal capacity, and altered expression of pluripotency markers. The observed CDKN2A expression changes are mediated by promoter methylation. These results highlight the potential role of CDKN2A as a therapeutic target and prognostic marker in glioblastoma.

Changes in CDKN2A gene expression can be used to predict the response of CRC patients to 5-FU therapy. Additionally, inhibiting CDKN2A activation with Villosol may present a new approach to overcoming 5-FU resistance in clinical settings.

CDKN2A upregulation extensively enhances the carcinogenesis and progression of SCLC.

P1, N=29, Active, not recruiting, ViMREX GmbH | Recruiting --> Active, not recruiting

Four histologically different HPV-independent penile precursor lesions can be assigned to 2 major genetic/biological pathways with characteristic highly differentiated precursors requiring different clinical management decisions. These include d-PeIN in chronic inflammatory dermatoses, with p53 overexpression and TP53/CDKN2A mutations, and the p53 wild-type verrucous and verruciform precursors unassociated with dermatoses, but with mutations in oncogenes PIK3CA and HRAS.

Combining Pdgfra overexpression and Cdkn2a inhibition drives gliomagenesis in vivo.

p53 expression and CDKN2A deletion represent a reliable pretreatment prognostic factor that identifies patients who do not benefit from currently used immunochemotherapy-based therapies and who are candidates for diversified treatments with the aim of improving prognosis. The MIPIb represents a prognostic index that correlates well with these biological alterations and can be used in clinical practice as their surrogate.

Patient-derived tumor organoids showed a significant response to the suggested treatment, Olaparib, supporting the reliability of PATRIOT prediction. Our analysis identified patients characterized by MET overexpression suggesting crizotinib, a small-molecule tyrosine kinase inhibitor of the c-MET receptor, as sequencing-matched therapy. Tumor organoids showed sensitivity to crizotinib (IC50 5.74 M+/- 3.2), validating our initial predictions. In a separate cohort, tumor organoids generated from patients characterized by downregulation of CDKN2A were treated with Palbociclib, a CDK4/6 inhibitor.

P1, N=29, Recruiting, ViMREX GmbH | Not yet recruiting --> Recruiting

P1, N=29, Not yet recruiting, ViMREX GmbH

These included clinical ALL drugs dexamethasone and daunorubicin, proteasome inhibitor carfilzomib, BCL2/BCLxL inhibitor navitoclax, and histone deacetylase inhibitors romidepsin and pracinostat...Combination of idasanutlin with navitoclax exhibited both the greatest and most consistent synergistic interaction (δ = 24.7±8.7, n=11) of the candidate combinations (n=10) across an extensive landscape of dose combinations; additionally alluding to synergy indiscriminate of ALL subtype...Together, we provide strong evidence that concurrent targeting of MDM2-p53 binding and BCL2/BCLxL leads to potent and synergistic enhancement of apoptotic cell death in a range of high-risk ALL subtypes. The proposed combination of two clinical-stage compounds could have considerable positive clinical impact for the treatment of adult ALL.

Experimental therapy aimed at inhibition of CDK by palbociclib and anti-apoptotic BCL-2 proteins using venetoclax, S63845 and A1155463 was performed on nine MCL cell lines and four patient-derived xenograft (PDX) models from patients with R/R MCL. Our data strongly support investigation of palbociclib in combination with venetoclax as an innovative treatment strategy for chemoresistant MCL patients without RB1 deletion. Although we demonstrated that palbociclib increases pro-apoptotic mitochondrial priming and induces metabolic stress, the detailed contribution of these changes to the observed synergy are under investigation.

Overexpression of 16ink4a in cardiac fibroblasts can ameliorate cardiac dysfunction and attenuate pathological cardiac remodeling in mice after MI by regulating the p16ink4a/CDK4/pRb pathway.

This study represents the largest cohort of Turkish patients with HNSCC characterized according to HPV status and p16INK4A expression. Our data suggest that HPV16 infection, along with smoking, contribute to the development of HNSCC.

P1, N=3, Terminated, University Hospital Heidelberg | N=18 --> 3 | Trial completion date: Oct 2021 --> Jun 2021 | Recruiting --> Terminated | Trial primary completion date: Oct 2021 --> Jun 2021; Organizational reasons

Our findings emphasize that the use of p16 as a surrogate of HPV positivity was unsuccessful in approximatively 8 % of cases analysed in our series. Indeed, p16 IHC showed a sensitivity of 100 % and a specificity of 71 %, with a positive predictive value (PPV) of 54 % and a negative predictive value of 100 %; when considering high intensity, p16 IHC showed a sensitivity of 100 %, a specificity of 89 %, with a PPV of 75 % and NPV of 100 %. Since HPV positivity could represent a relevant prognostic and predictive value, the correct characterization offered by this approach appears to be of paramount importance.

For pathologists, these variables in grade 2 tumors can be adjunctive aid for reaching an agreement to diagnose the grade of EOC patients.Footnotes1 A. Geissel and J. L. Griffin, “Preparation of nuclei for flow cytometry,” in AFIP Advances in Laboratory Methods in histology and Pathology, ed. Mikel UV (Washington DC: American Registry of Pathology, 1944), 111-121.

penile cancer positive for p16INK4a shows a trend for better survival, although the most relevant factor is nodal staging.

Our data highlights that HPV16, in particular the A2 sublineage, followed by A1 and D2 sublineages are the major agents associated with HNSCCs in Iran. Based on HPV16 predominance and its lineage distribution pattern, it seems that the prophylactic vaccines developed for cervical cancer prevention could also be applicable for the prevention of HPV-related HNSCCs in our population.

CDK4/6 inhibitor palbociclib showed an anti-tumor effect in vitro and in vivo xenograft model of CDKN2A loss gastric and breast cancer. Our results suggest that palbociclib has therapeutic potential for the treatment of not only breast cancer but also gastric cancer, not limited to a hormone-positive breast cancer type. Our results provide a rationale for the future clinical trials of palbociclib in the treatment of breast cancers.

Our results indicate a risk of misclassification of patients with otherOPSCC and low TNM-8 stage. We suggest that p16 should only be evaluated in TSCC/BOTSCC and that patients with otherOPSCC should all be staged as patients with HPV-unrelated (p16-) OPSCC.

p16INK4a positivity presented a high correlation to HPV 16 DNA detection, reinforcing its use as a surrogate marker for HPV-driven cancers. Infection with EBV was quite frequent and its role in epithelial penile oncogenesis needs to be demonstrated.

"The agreement observed between positives and negatives for HPV-DNA and p16 INK4A was 93.8% and a ki of 0.848. Conclusions The AmpFire HPV Tests are simple sample-to-answer and low cost assays for detection and genotyping of HPV in HN FFPE samples."

The multiplex HPV RNA ISH /p16 IHC results in the series both of the cervical cancers and the oral-oropharyngeal cancers were fully concordant with the previous results achieved through the classic p16 IHC and HPV RNA scope carried out on two different slides. Our results suggesting several advantages of this technical approach, namely an easy interpretation fully in the light field, the feasibility in formalin-fixed paraffin-embedded tissue sections, complete automation and a potential wide spreadable for routine testing in several clinical laboratories.

CDKN2A inhibits cell proliferation and invasion in cervical cancer through LDHA-mediated AKT-mTOR pathway.

These results collectively indicate that MDS-MSCs and MM-MSCs have common and different alterations at various degrees. Hence, it is necessary to evaluate their alteration status using representative markers such as CDKN2A expression.

The molecular biomarker p16INK4a can be a good candidate for the early diagnosis and prognosis of cervical cancer in HPV-infected patients. Considering the increase in the expression level of p16INK4a in cancer and precancer tissues, p16INK4a may be used for early detection of cervical cancer.

P1, N=18, Recruiting, University Hospital Heidelberg