Extracellular Polysaccharide from Rhizopus nigricans Inhibits Hepatocellular Carcinoma via miR-494-3p/TRIM36 Axis and Cyclin E Ubiquitination.

Background and Aims: This study was designed to uncover the mechanism for extracellular polysaccharide (EPS1-1)-mediated effects on hepatocellular carcinoma (HCC) development. Methods: HCC cells were treated with EPS1-1, miR-494-3p mimic, sh-TRIM36, and pcDNA3.1-TRIM36. The levels of miR-494-3p and TRIM36 were measured in normal hepatocytes, THLE-2, and HepG2 and HuH7HCC cell lines, along with the protein expression of cyclin D/E and p21. The proliferation, cell cycle, and apoptosis of HCC cells were assayed. The interactions between miR-494-3p and TRIM36, and between TRIM36 and cyclin E were assessed. Finally, the expression and localization of TRIM36 and cyclin E were monitored, and tumor apoptosis was detected, in tumor xenograft model. Results: EPS1-1 suppressed HCC cell proliferation and cyclin D/E expression and promoted apoptosis and p21 expression. miR-494-3p was upregulated and TRIM36 was downregulated in HCC cells. Transfection with miR-494-3p mimic or sh-TRIM36 facilitated HCC cell proliferation and the expression of cyclin D/E protein but they inhibited apoptosis and p21 expression in the presence of EPS1-1. Overexpression of TRIM36 further consolidated EPS1-1-mediated inhibition of HCC proliferation, cyclin D/E, and the promotion of apoptosis and p21 expression. Those effects were reversed by miR-494-3p overexpression. TRIM36 was a target gene of miR-494-3p, and TRIM36 induced cyclin E ubiquitination. EPS1-1 suppressed cyclin E expression, promoted TRIM36 expression and tumor apoptosis, all of which were abrogated by increasing the expression of miR-494-3p in vivo. Conclusions: EPS1-1 protected against HCC by limiting its proliferation and survival through the miR-494-3p/TRIM36 axis and by inducing cyclin E ubiquitination.

Tumor microenvironment-responsive multifunctional nanoplatform based on MnFe2O4-PEG for enhanced magnetic resonance imaging-guided hypoxic cancer radiotherapy.

Radiotherapy occupies an essential position in curing and palliating a wide range of solid tumors based on DNA damage responses to eradicate cancer cells. However, the tumor microenvironment generally exhibits the characteristics of hypoxia and glutathione overexpression, which play a critical role in radioresistance, to prevent irreparable breaks to DNA and necrocytosis of cancer cells. Herein, polyethylene glycol (PEG) functionalized manganese ferrite nanoparticles (MnFe2O4-PEG) are designed to enable self-sufficiency of oxygen by continuously catalyzing the decomposition of endogenous hydrogen peroxide. Simultaneously, the nano-platform can consume GSH to reduce the loss of reactive oxygen species in radiotherapy and achieve better therapeutic effects at the cellular and animal levels. In addition, the MnFe2O4-PEG could act as an optimal T1- and T2-weighted contrast medium for tumor-specific magnetic resonance imaging. This work proposes a systematically administered radiosensitizer that can selectively reside in tumor sites via the enhanced permeability and retention effect to relieve hypoxia and reduce GSH concentration, combined with dual-mode magnetic resonance imaging, achieving precise and effective image-guided tumor therapy.

Radiomics in predicting tumor molecular marker P63 for non-small cell lung cancer.

OBJECTIVE: To establish a radiomics signature based on CT images of non-small cell lung cancer (NSCLC) to predict the expression of molecular marker P63.
 Methods: A total of 245 NSCLC patients who underwent CT scans were retrospectively included. All patients were confirmed by histopathological examinations and P63 expression were examined within 2 weeks after CT examination. Radiomics features were extracted by MaZda software and subjective image features were defined from original non-enhanced CT images. The Lasso-logistic regression model was used to select features and develop radiomics signature, subjective image features model, and combined diagnostic model. The predictive performance of each model was evaluated by the receiver operating characteristic (ROC) curve, and compared with Delong test.
 Results: Of the 245 patients, 96 were P63 positive and 149 were P63 negative. The subjective image feature model consisted of 6 image features. Through feature selection, the radiomics signature consisted of 8 radiomics features. The area under the ROC curves of the subjective image feature model and the radiomics signature in predicting P63 expression statue were 0.700 and 0.755, respectively, without a significant difference (P>0.05). The combined diagnostic model showed the best predictive power (AUC=0.817, P<0.01).
 Conclusion: The radiomics-based CT scan images can predict the expression status of NSCLC molecular marker P63. The combination of the radiomics features and subjective image features can significantly improve the predictive performance of the predictive model, which may be helpful to provide a non-invasive way for understanding the molecular information for lung cancer cells.

Radiomics and its advances in hepatocellular carcinoma.

Liver cancer is the second leading cause of cancer-related death worldwide, so early detection and prediction for response to treatment is of great benefit to hepatocellular carcinoma (HCC) patients. Currently, needle biopsy and conventional medical imaging play a significant and basic role in HCC patients' management, while those two approaches are limited in sample error and observer-dependence. Radiomics can make up for this deficiency because it is an emerging non-invasive technic that is capable of getting comprehensive information relevant to tumor situation across spatial-temporal limitation. The basic procedure for radiomics includes image acquisition, region of interest segmentation and reconstruction, feature extraction, selection and classification, and model building and performance evaluation. The current advances and potential prospect of radiomics in HCC studies are involved in diagnosis, prediction for response to treatment, prognosis evaluation and radiogenomics.

EphA10 and EphB3 are prognostic markers in gallbladder squamous cell/adenosquamous carcinomas and adenocarcinomas.

AIMS: Squamous cell/adenosquamous carcinomas (SC/ASC) are rare subtypes of gallbladder cancers (GBCs). Clinical characteristics of SC/ASC have not been well documented, and no biological markers of GBC carcinogenesis, progression and prognosis are available. METHODS: We detected EphA10 and EphB3 expression in 69 SC/ASCs and 146 adenocarcinomas (ACs) with EnVision immunohistochemistry. RESULTS: The percentage of cases with a patient age of > 45 years, lymph node metastasis and invasion was significantly higher in the SCs/ASCs compared with the ACs (P < 0.05). The positive expression of EphA10 and negative expression of EphB3 were significantly higher in the cases of SC/ASC and AC than in chronic cholecystitis (P < 0.01). The positive expressions of EphA10 and negative expression of EphB3 were significantly higher in the cases of poorly differentiation, large tumor size, high TNM stage, lymph node metastasis, invasion and no resection (only biopsy) of SC/ASC and AC. The negative correlation was found between EphA10 and EphB3 expression in SC/ASC and AC (P < 0.01). The univariate Kaplan-Meier analysis showed that positive EphA10 and negative EphB3, differentiation, tumor size, TNM stage, lymph node metastasis, invasion and surgical curability, is closely associated with a decreased overall survival in SC/ASC and AC patients (P < 0.05 or P < 0.01). The multivariate Cox regression analysis identified that positive EphA10 and negative EphB3 expression are independent factors for a poor-prognosis in SC/ASC and AC patients. The AUC for EphA10 and EphB3 showed might have role for carcinogenesis and progression of SC/ASC and AC. CONCLUSIONS: The present study indicates that positive EphA10 and negative EphB3 expression are closely associated with the pathogenesis, clinical, pathological and biological behaviors, and poor prognosis in gallbladder cancer.

Hepatic perivascular epithelioid cell tumor: Case report and brief literature review.

RATIONAL: Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm which expresses both myogenic and melanocytic markers. PEComas are found in a variety locations in the body, but up to now only approximately 30 cases about hepatic perivascular epithelioid cell tumor are reported in English language worldwide. PATIENT CONCERNS: A 32-year-old woman was admitted in our hospital with intermittent right upper quadrant pain for 1 month and recent (1 day) progressive deterioration. DIAGNOSES: Based on the results of the laboratory examinations and the findings of the computed tomography, the diagnosis of hepatic hamartoma or the hepatocecullar carcinoma with hemorrhage was made. INTERVENTIONS: The patient underwent a segmentectomy of the liver, and the finally diagnosis of hepatic PEComa was made with immunohistochemical confirmation with HMB-45 and SMA. OUTCOMES: There is no clinical or radiographic evidence of recurrence 9 months after surgery. LESSONS: This kind of tumor is extremely rare and the natural history of PEComa is uncertain, as the treatment protocol for hepatic PEComa has not reached a consensus. But the main treatment of the disease may be surgical resection. Only after long term follow-up can we know whether the tumor is benign or malignant. It appears that longer clinical follow-up is necessary in all patients with hepatic PEComas.