TP53 (Tumor protein P53)

Accordingly, a machine-learning approach identifies a composite molecular and functional signature that best predicts responses of diverse intracranial glioma models to standard-of-care therapies combined with ABBV-155, a clinical drug targeting intrinsic apoptosis. This work demonstrates how complementary functional and molecular data can robustly predict therapy-induced cell death.

In conclusion, the morphological heterogeneity of HCC, directly linked to molecular heterogeneity, is associated with prognosis. This strongly supports the specification of the different HCC subtypes in our reports.

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Conclusion In young adult GBM patients, especially those ≤ 40 years of age with long survival, attention should be given to the development of systemic metastases. Metastasis can be the result of multiclonal gene mutations, in which proliferation- and invasion-related gene changes, such as oncogene or tumor suppressor gene mutations and epithelial-mesenchymal transition-related genes, may play an important role in metastasis.

We have developed an oncolytic adenovirus OBP-702 carrying the tumor suppressor gene p53 and have demonstrated its therapeutic potential to induce cytopathic effect and activate antitumor immunity via p53 induction. In this study, we investigated the combined effect of p53-transduced DC vaccine and OBP-702 in colorectal cancer.

It might be a predictive and prognostic biomarker or therapeutic target to achieve the desired clinical benefits. Moreover, we discuss potential strategies to implement targeted therapies in terms of SMAD4 genetic status.

We show that the G334R variant retains the ability to interact with the SP1 transcription factor and contributes to the transactivation of joint SP1-p53 target genes. The combined evidence indicates that G334R is a unique oligomerization domain mutant that retains some tumor suppressor function.

Overlap of the Oncopig LC transcriptome with human LC transcriptome was noted. This pig model is expected to have high clinical translatability to the human LC patient.

This review will discuss the cellular responses controlled by p53 that contribute to tumour suppression, p53 mutant lung cancer mouse models and characterisation of p53 mutant lung cancer. Furthermore, we discuss potential approaches of targeting mutant p53 for the treatment of lung cancer.

BRCA1/BRCA2 carriers contained a small percentage of cells with extreme aneuploidy, featuring loss of TP53, BRCA1/BRCA2 LOH and multiple breast cancer-associated CNAs. Our findings suggest that CNAs arising in normal luminal breast epithelium are precursors to clonally expanded tumor genomes.

The HFD groups subjected to RFM had significantly lower Insulin-like growth factor 1 (IGF-1) and mechanistic target of rapamycin (mTOR) serum, whereas AMPK, anti-inflammatory, and antioxidative stress serum levels were significantly higher...The data indicate that RFM can improve longevity and metabolic biomarkers and reduce pro-inflammation and oxidative stress. Also, RFM improves anti-inflammatory and antioxidant markers in HFD-induced obese rats.

No abstract available

Finding and confirming these biomarkers is essential for improving early detection, tracking the course of the disease, and directing focused treatments. As research progresses, combining molecular, genetic, and environmental insights might improve lung cancer care, prevention, and early diagnosis, thereby lowering the disease's worldwide burden.

the mutational landscape of SPTCL is broader than previously anticipated. We describe, for the first time, the involvement of the TP53 (P72R) pathogenic variant in this subgroup of tumors, consider the possible role of different genetic backgrounds in the development of SPTCL, and conclude that LEP does not follow the same pathogenic pathway as SPTCL.

YAP1 and LEUTX have been implicated in tumorigenesis of various neoplasms, and YAP1 fusion genes are an emerging oncogenic entity in a variety of malignancies. In this study we highlight the importance of whole-genome characterization of rare and unclassified tumors to identify biologic mechanisms and potential therapeutic targets.

The study highlights the genetic diversity in Persian patients with metastatic colon adenocarcinoma and demonstrated that APC and TP53 variants were the most prevalent, while KRAS and ERBB2 variants were associated with specific tumor sites. These findings provide a basis for personalized treatment strategies in CRC among Persian population.

The incorporation of amino acids at codons 127, 128, or 129 generally result in a p53 protein that is predicted to be 'unfolded' or inactive as defined by molecular dynamic simulations presumably because the production of mixed wild-type p53 and mutant oligomers are known to be inactive through dominant negative effects of the mutation. The data highlight the need to not only produce novel small molecules that can readthrough PTCs or C-terminal termination codons, but also the need to design methods to insert the required amino acid at the position that could result in a 'wild-type' functional protein.

Laboratory measures and utilizing NGS assay when needed, could be implemented when encountering such problematic "low-level" MDM2 amplification specimens to avoid misdiagnosis and misuse of targeted therapy. Future studies are needed to better characterize and investigate such findings.

The formation of Δ133p53α and p53 complexes increases at later DDR stages. We propose that Δ133p53α isoforms regulate p53 conformation as part of the normal p53 biology, modulating p53 activity and thereby adapting the cellular response to the cell signals.

Current treatment strategies, including conventional chemotherapy, hypomethylating agents, and venetoclax-based therapies, have shown limited efficacy in TP53-mutated AML, with low response rates and poor overall survival...Novel therapeutic modalities, including immune-based therapies, did show promise in early-phase studies but did not translate into effective therapies in randomized controlled trials. This review provides a comprehensive overview of TP53 mutations in AML, outcomes based on allelic burden, clinical implications, and therapeutic challenges.

Co-treatment with SY-5609 and ruxolitinib was synergistically lethal in HEL, SET2 and PD post-MPN-sAML cells.  A CRISPR screen in SET2 and HEL cells revealed BRD4, CBP and p300 as co-dependencies with SY-5609 treatment. Accordingly, co-treatment with SY-5609 and the BETi OTX015 or pelabresib or with the CBP/p300 inhibitor GNE-049 was synergistically lethal in MPN-sAML cells (including those exhibiting TP53 loss). Finally, in the HEL-Luc/GFP xenograft model, compared to each agent alone, co-treatment with SY-5609 and OTX015 reduced post-MPN-sAML burden and improved survival without inducing host toxicity. These findings demonstrate promising preclinical activity of the CDK7i-based combinations with BETi or HATi against advanced-MPNs, including post-MPN-sAML.

The MiCBO-TF model represents a powerful platform for both mechanistic investigations and the development of precision medicine approaches for DMG.

Although the presence of CH did not directly predict MN-pCT development in patients with BC, CT induced changes in CH genes. Further studies are required to determine the role of specific CH variants in the risk of MN-pCT and their potential as predictive biomarkers.

Glioblastoma undergoes heterogeneous genetic, epigenetic, and cellular evolution that underlies prognostically different treatment responses.

Overexpression of MDM2 is a novel resistant mechanism to Osimertinib in EGFR mutant NSCLC. MDM2 utilizes its E3 ligase activity to provoke FBW7 destruction and sequentially leads to MCL-1 stabilization. Cancer cells with aberrant MDM2 state are refractory to apoptosis induction and elicit a resistant phenotype to Osimertinib. Therefore, targeting MDM2 would be a feasible approach to overcome resistance to Osimertinib in EGFR mutant NSCLC.

DNA nanoparticles show promise for improving mRNA vaccine delivery and efficacy. Further optimization of these nanoparticles could lead to highly effective mRNA vaccine carriers with broad applications.

Our study provides a comprehensive characterization of the genomic landscape and clonal evolution in OCCC within a substantial cohort. These findings unveil potentially actionable molecular alterations that could be leveraged to develop targeted therapies.

Therefore, a good understanding regarding the genetic and epigenetic modifications is not only essential for the diagnosis and prognosis of TC, but also for the development of novel therapeutics. In this review, most of the major TC-related genetic and epigenetic modifications and their potential as biomarkers for TC diagnosis and prognosis have been extensively discussed.

Additionally, DI-SeNPs exhibited antimicrobial activity against various bacteria and fungi. These findings suggest that DI-SeNPs possess significant anticancer and antimicrobial properties, mediated through mechanisms involving ROS generation, cell cycle arrest, and apoptosis induction.

In conclusion, pedHGG-RTK2A/B tumors are characterized by highly diffuse-infiltrating growth patterns and specific radiological and histo-molecular features. By comprehensively characterizing methylation-based tumors, the chance to develop specific and effective therapy concepts for these detrimental tumors increases.

Inhibition of WEE1, CHK1 and ATR selectively inhibits the growth of cells deficient in CDK12. Our data suggest that large TDs in cancer form as a result of TRCs and their presence can be used as a biomarker for prognosis and treatment.

Incubation with derivative 13 resulted in the induction of oxidative stress and triggered a cascade of cellular defence proteins that failed in the face of such an active compound. In addition, the results showed an inhibition of the GLUT-1 glucose transporter, which is extremely important in the context of anti-cancer activity.

Thereby, MDM4 enhances the stability of GPX4 protein, inhibiting ferroptosis, increasing the resistance of colon cancer patients to chemotherapy, and promoting colon cancer progression. These findings elucidate the ferroptosis inhibition effect of MDM4 via regulating TRIM21/GPX4 on p53-mutated colon cancer and provide a potential therapeutic strategy for colon cancer therapy.

We propose a novel RPM mouse model as a suitable system to mimic MMR-defective SCLC and tumors with high TMB. We provide in vivo evidence that Msh2 deficiency enhances ICI sensitivity. These findings could contribute to stratifying SCLC patients to immunotherapy, thereby improving treatment outcomes.

All five patients died of disease, with a mean overall survival of 41 months from the first metastatic disease and 12 months from acquisition of RB1/TP53 co-alteration. Our data demonstrate that low-grade NET can progress via the acquisition of both TP53 and RB1 alteration, similar to NEC, but whether this represents a transformation from NET to NEC remains unclear.

Our data indicate that sDNA could aid in the monitoring of patients' follow-up as low-frequency somatic mutations could be assessed from the saliva of HNSCC patients. Prospectively, these results suggest that salivary-based liquid biopsy might pave the way for personalized molecular therapies based on mutational data.

Validation of these genes was achieved through GEPIA and western blotting. Collectively, our findings provide insights into the functional landscape of liver cancer-related genes, shedding light on the molecular mechanisms driving disease progression and highlighting potential targets for therapeutic intervention.

Finally, we discovered co-mutated gene pairs and TP53 p.R282W mutations related to treatment outcomes, highlighting their gender-specific differences. This study identified several molecular biomarkers related to cancer immunotherapy outcomes in terms of mutational signatures, molecular subtypes, and mutated genes, and explored their gender-relatedness in order to provide clues and basis for clinical treatment efficacy evaluation and patient selection.

Through this endeavor, we identified two novel genes, CNTNAP5 and GATA6, implicated in CRC carcinogenesis. Overall, our findings reveal convincing biomarkers markers for detecting CRAs with a propensity for CRC development, highlighting the importance of early genetic screening in CRC prevention.

Moreover, a heightened awareness urging the adoption of advanced diagnostic techniques and collaborative approaches is necessary among clinicians and researchers. We aim to contribute to the ongoing discourse in gastrointestinal oncology, emphasizing the importance of recognizing and addressing the complexities associated with rare cancer subtypes such as CRA.

While Rad-score of Ki-67 expression status in the training group obtained the top accuracy, sensitivity, specificity, and PPV with values of 0.85, 0.80, 0.92, and 0.93. Preoperative MRI-based radiomics analysis has the ability to noninvasively assess the postoperative Ki-67, p53, and EGFR of rectal cancer.

In the Korean cohort, ICIs were most effective in MSI and EBV cases, showing disease control rates of 100%, compared to 62.9% in GS and 12.5% in CIN subtypes. The NGS method successfully maps the mutational landscape of GC, providing a practical TCGA classification surrogate to optimize patient-specific treatment strategies.