TP53 is a critical tumor-suppressor gene that is mutated in more than half of all human cancers. Mutations in TP53 not only impair its antitumor activity, but also confer mutant p53 protein oncogenic properties. The p53-targeted therapy approach began with the identification of compounds capable of restoring/reactivating wild-type p53 functions or eliminating mutant p53. Treatments that directly target mutant p53 are extremely structure and drug-species-dependent. Due to the mutation of wild-type p53, multiple survival pathways that are normally maintained by wild-type p53 are disrupted, necessitating the activation of compensatory genes or pathways to promote cancer cell survival. Additionally, because the oncogenic functions of mutant p53 contribute to cancer proliferation and metastasis, targeting the signaling pathways altered by p53 mutation appears to be an attractive strategy. Synthetic lethality implies that while disruption of either gene alone is permissible among two genes with synthetic lethal interactions, complete disruption of both genes results in cell death. Thus, rather than directly targeting p53, exploiting mutant p53 synthetic lethal genes may provide additional therapeutic benefits. Additionally, research progress on the functions of noncoding RNAs has made it clear that disrupting noncoding RNA networks has a favorable antitumor effect, supporting the hypothesis that targeting noncoding RNAs may have potential synthetic lethal effects in cancers with p53 mutations. The purpose of this review is to discuss treatments for cancers with mutant p53 that focus on directly targeting mutant p53, restoring wild-type functions, and exploiting synthetic lethal interactions with mutant p53. Additionally, the possibility of noncoding RNAs acting as synthetic lethal targets for mutant p53 will be discussed.

Hepatocellular carcinoma (HCC) is the most common subtype of liver cancer, and assessing its histopathological grade requires visual inspection by an experienced pathologist. In this study, the histopathological H&E images from the Genomic Data Commons Databases were used to train a neural network (inception V3) for automatic classification. According to the evaluation of our model by the Matthews correlation coefficient, the performance level was close to the ability of a 5-year experience pathologist, with 96.0% accuracy for benign and malignant classification, and 89.6% accuracy for well, moderate, and poor tumor differentiation. Furthermore, the model was trained to predict the ten most common and prognostic mutated genes in HCC. We found that four of them, including CTNNB1, FMN2, TP53, and ZFX4, could be predicted from histopathology images, with external AUCs from 0.71 to 0.89. The findings demonstrated that convolutional neural networks could be used to assist pathologists in the classification and detection of gene mutation in liver cancer.

Synthetic lethality is a lethal phenomenon in which the occurrence of a single genetic event is tolerable for cell survival, whereas the co-occurrence of multiple genetic events results in cell death. The main obstacle for synthetic lethality lies in the tumor biology heterogeneity and complexity, the inadequate understanding of synthetic lethal interactions, drug resistance, and the challenges regarding screening and clinical translation. Recently, DNA damage response inhibitors are being tested in various trials with promising results. This review will describe the current challenges, development, and opportunities for synthetic lethality in cancer therapy. The characterization of potential synthetic lethal interactions and novel technologies to develop a more effective targeted drug for cancer patients will be explored. Furthermore, this review will discuss the clinical development and drug resistance mechanisms of synthetic lethality in cancer therapy. The ultimate goal of this review is to guide clinicians at selecting patients that will receive the maximum benefits of DNA damage response inhibitors for cancer therapy.

The updated meta-analysis first confirms that LCBDE+LC is superior to pre-EST+LC both in perioperative safety and short- and long-term postoperative efficacy, which should be considered as optimal treatment choice for cholecysto-choledocholithiasis.

<b><i>Background:</i></b> The preoperative selection of patients with intermediate-stage hepatocellular carcinoma (HCC) who are likely to have an objective response to first transarterial chemoembolization (TACE) remains challenging. <b><i>Objective:</i></b> To develop and validate a clinical-radiomic model (CR model) for preoperatively predicting treatment response to first TACE in patients with intermediate-stage HCC. <b><i>Methods:</i></b> A total of 595 patients with intermediate-stage HCC were included in this retrospective study. A tumoral and peritumoral (10 mm) radiomic signature (TPR-signature) was constructed based on 3,404 radiomic features from 4 regions of interest. A predictive CR model based on TPR-signature and clinical factors was developed using multivariate logistic regression. Calibration curves and area under the receiver operating characteristic curves (AUCs) were used to evaluate the model’s performance. <b><i>Results:</i></b> The final CR model consisted of 5 independent predictors, including TPR-signature (<i>p</i> &#x3c; 0.001), AFP (<i>p</i> = 0.004), Barcelona Clinic Liver Cancer System Stage B (BCLC B) subclassification (<i>p</i> = 0.01), tumor location (<i>p</i> = 0.039), and arterial hyperenhancement (<i>p</i> = 0.050). The internal and external validation results demonstrated the high-performance level of this model, with internal and external AUCs of 0.94 and 0.90, respectively. In addition, the predicted objective response via the CR model was associated with improved survival in the external validation cohort (hazard ratio: 2.43; 95% confidence interval: 1.60–3.69; <i>p</i> &#x3c; 0.001). The predicted treatment response also allowed for significant discrimination between the Kaplan-Meier curves of each BCLC B subclassification. <b><i>Conclusions:</i></b> The CR model had an excellent performance in predicting the first TACE response in patients with intermediate-stage HCC and could provide a robust predictive tool to assist with the selection of patients for TACE.

Objective To assess the feasibility, safety, and potential benefits of laparoscopy-assisted living donor hepatectomy (LADH) in comparison with open living donor hepatectomy (ODH) for liver transplantation. Background LADH is becoming increasingly common for living donor liver transplant around the world. We aim to determine the efficacy of LADH and compare it with ODH. Methods A systematic search on PubMed, Embase, Cochrane Library, and Web of Science was conducted in May 2017. Results Nine studies were suitable for this analysis, involving 979 patients. LADH seemed to be associated with increased operation time (WMD = 24.85 min; 95% CI: −3.01~52.78, P = 0.08), less intraoperative blood loss (WMD = −59.92 ml; 95% CI: −94.58~−25.27, P = 0.0007), similar hospital stays (WMD = −0.47 d; 95% CI: −1.78~0.83, P = 0.47), less postoperative complications (RR = 0.70, 95% CI: 0.51~0.94, P = 0.02), less analgesic use (SMD = −0.22; 95% CI: −0.44~−0.11, P = 0.04), similar transfusion rates (RR = 0.82; 95% CI: 0.24~3.12, P = 0.82), and similar graft weights (WMD = 7.31 g; 95% CI: −23.45~38.07, P = 0.64). Conclusion Our results indicate that LADH is a safe and effective technique and, when compared to ODH.

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BackgroundSagittal spinopelvic alignment changes associated with degenerative facet joint arthritis have been assessed in a few studies. It has been documented that patients with facet joint degeneration have higher pelvic incidence, but the relationship between facet joint degeneration and other sagittal spinopelvic alignment parameters is still disputed. Our purpose was to evaluate the correlation between the features of sagittal spinopelvic alignment and facet joint degeneration.MethodsImaging data of 140 individuals were retrospectively analysed. Lumbar lordosis, pelvic tilt (PT), pelvic incidence (PI), sacral slope, and height of the lumbar intervertebral disc were measured on lumbar X-ray plates. Grades of facet joint degeneration were evaluated from the L2 to S1 on CT scans. Spearman’s rank correlation coefficient and Student’s t-test were used for statistical analyses, and a P-value <0.05 was considered statistically significant.ResultsPI was positively associated with degeneration of the facet joint at lower lumbar levels (p < 0.001 r = 0.50 at L5/S1 and P = 0.002 r = 0.25 at L4/5). A significant increase of PT was found in the severe degeneration group compared with the mild degeneration group: 22.0° vs 15.7°, P = 0.034 at L2/3;21.4°vs 15.1°, P = 0.006 at L3/4; 21.0° vs 13.5°, P = 0.000 at L4/5; 20.8° vs 12.1°, P = 0.000 at L5/S1.ConclusionOur results indicate that a high PI is a predisposing factor for facet joint degeneration at the lower lumbar spine, and that severe facet joint degeneration may accompany with greater PT at lumbar spine.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-016-1193-6) contains supplementary material, which is available to authorized users.