An overview of the functions of p53 and drugs acting either on wild- or mutant-type p53.

TP53, also known as the "guardian of the genome," is an important tumor suppressor gene. It is encoded by the human genome and is associated with the development of diverse cancers. The p53 protein, encoded by TP53, functions in the cell to monitor DNA damage and prompts the cell to respond appropriately. When DNA is damaged, p53 halts the cell cycle, allowing cells to enter the repair state. If the repair is ineffective, p53 induces cell death via apoptosis. This prevents DNA damage transmission during cell division and reduces cancer risk. However, the p53 gene mutation compromises its function. This leads to the inability of cells to respond properly to DNA damage, which may result in cancer development. Mutations in p53 are widespread in diverse cancers, especially highly prevalent cancers, including breast, colon, and lung cancers. Despite the association between p53 mutations and cancer, researchers have discovered drugs and treatments that may reactivate mutated p53 function. Therefore, p53 remains an important area of research in cancer treatment and holds promise as a new direction for cancer therapy. In summary, TP53 is a vital tumor suppressor gene responsible for monitoring DNA damage and prompting cells to respond appropriately. This article summarizes drugs related to p53 and diverse strategies for discovering drugs that act on either wide or mutant p53. Herein, p53 is categorized into two types: wild and mutant type. Drugs are also classified according to diverse treatment strategies, enabling readers to differentiate between the two types of p53 and aiding in selecting the appropriate research direction. Additionally, this review offers a valuable reference for drug design.

Nomogram for Preoperative Estimation of Cervical Lymph Node Metastasis Risk in Papillary Thyroid Microcarcinoma.

Objective: Accurate preoperative identification of cervical lymph node metastasis (CLNM) is essential for clinical management and established of different surgical protocol for patients with papillary thyroid microcarcinoma (PTMC). Herein, we aimed to develop an ultrasound (US) features and clinical characteristics-based nomogram for preoperative diagnosis of CLNM for PTMC. Method: Our study included 552 patients who were pathologically diagnosed with PTMC between January 2015 and June 2019. All patients underwent total thyroidectomy or lobectomy and divided into two groups: CLNM and non-CLNM. Univariate and multivariate analysis were performed to examine risk factors associated with CLNM. A nomogram comprising the prognostic model to predict the CLNM was established, and internal validation in the cohort was performed. Results: CLNM and non-CLNM were observed in 216(39.1%) and 336(60.9%) cases, respectively. Seven variables of clinical and US features as potential predictors including male sex (odd ratio [OR] = 1.974, 95% confidence interval [CI], 1.243-2.774; P =0.004), age < 45 years (OR = 4.621, 95% CI, 2.160-9.347; P < 0.001), US-reported CLN status (OR = 1.894, 95% CI, 0.754-3.347; P =0.005), multifocality (OR = 1.793, 95% CI, 0.774-2.649; P =0.007), tumor size ≥ 0.6cm (OR = 1.731, 95% CI,0.793-3.852; P =0.018), ETE (OR = 3.772, 95% CI, 1.752-8.441;P< 0.001) and microcalcification (OR = 2.316, 95% CI, 1.099-4.964; P < 0.001) were taken into account. The predictive nomogram was established by involving all the factors above used for preoperative prediction of CLNM in patients with PTCM. The nomogram model showed an AUC of 0.839 and an accuracy of 77.9% in predicting CLNM. Furthermore, the calibration curve demonstrated a strong consistency between nomogram and clinical findings in prediction CLNM for PTMC. Conclusions: The nomogram achieved promising results for predicting preoperative CLNM in PTMC by combining clinical and US risk factor. Our proposed prediction model is able to help determine an individual's risk of CLNM in PTMC, thus facilitate reasonable therapy decision making.