TP53 (Tumor protein P53)

P1/2, N=20, Recruiting, University Hospital Tuebingen | Trial completion date: Mar 2027 --> Feb 2029 | Trial primary completion date: Mar 2027 --> Jul 2028

ACD-RCC is a rare renal cell carcinoma that occurs in patients with end-stage renal disease and has unique morphological features. It is often associated with favorable prognosis and alterations in genes related to the MTOR/TSC pathway or chromatin modification.

BRCA2 is the most common gene with germline variations, while CDK12 is the most frequently mutated gene in somatic HRR variants. This study suggests that HRR gene testing in patients with high-risk HSPC would help identify those with more aggressive clinical features and guide prognostication and potential targeted therapeutic strategies.

ASK in children is a rare DICER1-related tumor, with distinct histologic features and biological behavior. The differential diagnosis includes anaplastic Wilms tumor, clear cell sarcoma of the kidney, etc. Integration of clinical manifestations, histology, immunohistochemistry, and molecular studies may be required to render correct diagnosis.

Oral Lm-based cancer vaccines targeting CRC elicit robust, widely disseminated, and persistent tumor-specific immune responses in mice. These vaccines limit CRC development when administered prophylactically and provide tumor control when administered therapeutically with ICI. Thus, oral delivery of Lm-based cancer vaccines coupled with ICI may provide improved control of CRC progression in clinical application.

Here, we employed an integrative biochemical approach combining a novel flux tracing method (using d17dihydrosphingosine) with in situ enzymatic activity assays in the context of treatment with Doxorubicin (Dox), a DNA-damaging agent causing well-established dose-dependent activation of p53...iv) With respect to inhibition of d17sphingomyelin synthesis, an investigation into ceramide transport to the Golgi identified the ceramide transport protein 1 (CERT1) as a novel target of Dox (reduction of protein and activity) and p53 (reduction of activity, particularly at low Dox). These observations underscore p53's prominent role as a master regulator of SPL metabolism, inducing major remodeling of cellular SPL metabolism with extensive and integrated effects on sphingolipid synthesis.

The findings suggest that Codonopsis pilosula may elicit antidepressant effects through a multi-component, multi-target, and multi-pathway approach, laying a foundation for further exploration and clinical utilization of Codonopsis pilosula in the prevention and treatment of depression.

These data provide an expanded understanding of the molecular underpinnings of EMCG-including the first description of a SMARCA4 frameshift variant in this entity-and demonstrate that while gastrointestinal marker immunoexpression is relatively common among endometrial carcinomas, strictly defined EMCG remains rare (<1%). As awareness of this entity grows, pathologists should take care not to over-interpret gastrointestinal marker expression as stand-alone evidence of an EMCG diagnosis.

Our findings demonstrated that the TMEM158-TGF-β pathway plays a central role in mediating the heightened sensitivity of TP53-deficient OS to USP14 inhibition. Targeting this pathway may represent a promising therapeutic strategy for precision treatment of osteosarcoma.

This study elucidated a previously unrecognized role of ENY2 in tumor growth, clarified the NPM1/MDM2/ p53-dependent mechanism of ENY2-mediated tumor cell growth suppression. We also provided a novel p53-independent RISC-IL11 nucleolar stress response pathway, which may provide a new target for the treatment of breast cancer.