The phosphatase and tensin homolog gene inserted between NP and P gene of recombinant New castle disease virus oncolytic effect test to glioblastoma cell and xenograft mouse model.

BACKGROUND: Glioblastoma is one of the most serious brain cancer. Previous studies have demonstrated that PTEN function disorder affects the causing and exacerbation of glioblastoma. Newcastle disease virus (NDV) has been studied as a cancer virotherapeutics. In this study, PTEN gene was delivered to glioblastoma by recombinant NDV (rNDV) and translated into protein at the cytoplasm of the glioblastoma. METHODS: We did comparison tests PTEN protein expression efficiency and oncolytic effect depend on the PTEN gene insertion site at the between NP and P genes and the between P and M gene. PTEN protein mRNA transcription, translation in glioblastoma cell, and functional PTEN protein effect of the rNDV in vitro and in vivo test performed using western blotting, RT-qPCR, MTT assay, and Glioblastoma xenograft animal model test. RESULTS: The result of this study demonstrates that rNDV-PTEN kills glioblastoma cells and reduces cancer tissue better than rNDV without the PTEN gene. In molecular immunological and cytological assays, PTEN expression level was high at located in the between NP and P gene, and PTEN gene was successfully delivered to the glioblastoma cell using rNDV and PTEN gene translated to functional protein and inhibits hTERT and AKT gene. CONCLUSIONS: PTEN gene enhances the oncolytic effect of the rNDV. And our study demonstrated that NP and P gene site is better than P and M gene site which is commonly and conventionally used. PTEN gene containing rNDV is a good candidate virotherapeutics for glioblastoma.

Dendritic spine anomalies and PTEN alterations in a mouse model of VPA-induced autism spectrum disorder.

Mounting evidence suggests that the etiology of autism spectrum disorders (ASDs) is profoundly influenced by exposure to environmental factors, although the precise molecular and cellular links remain ill-defined. In this study, we examined how exposure to valproic acid (VPA) during pregnancy is associated with an increased incidence of ASD. A mouse model was established by injecting VPA at embryonic day 13, and its behavioral phenotypes including impaired social interaction, increased repetitive behaviors and decreased nociception were observed at postnatal days 21-42. VPA-treated mice showed dysregulation of synaptic structure in cortical neurons, including a reduced proportion of filopodium-type and stubby spines and increased proportions of thin and mushroom-type spines, along with a decreased spine head size. We also found that VPA-treatment led to decreased expression of phosphate and tensin homolog (PTEN) and increased levels of p-AKT protein in the hippocampus and cortex. Our data suggest that there is a correlation between VPA exposure and dysregulation of PTEN with ASD-like behavioral and neuroanatomical changes, and this may be a potential mechanism of VPA-induced ASD.

Combining concurrent radiotherapy and immunotherapy for synergistic effects in recurrent endometrial cancer - A case report.

Endometrial cancer, also known as uterine cancer, is the second most common cancer affecting women globally and the fourth most prevalent in the United States (US). Treatment often involves a combination of surgery, radiotherapy and chemotherapy depending on the severity. In this case report, we present two patients with relapsed endometrial carcinomas, who responded positively to combined radiotherapy and immunotherapy followed by maintenance immunotherapy. Given the worsening prognoses associated with recurrent endometrial cancers, these two cases warrant the further exploration of the concurrent administration of immunotherapy and radiation therapy in the context of clinical trials.

Structural Protein Analysis of Driver Gene Mutations in Conjunctival Melanoma.

In recent years, there has been tremendous enthusiasm with respect to detailing the genetic basis of many neoplasms, including conjunctival melanoma (CM). We aim to analyze five proteins associated with CM, namely BRAF, NRAS, c-KIT, NF1, and PTEN. We evaluated each protein for its intrinsically disordered protein regions (IDPRs) and its protein-protein interactions (PPI) with the Predictor of Natural Disordered Protein Regions (PONDR®) and the Search Tool for the Retrieval of Interacting Genes (STRING®). Our PONDR® analysis found high levels of IDPRs in all five proteins with mutations linked to CM. The highest levels of IDPRs were in BRAF (45.95%), followed by PTEN (31.76%), NF1 (22.19%), c-KIT (21.82%), and NRAS (14.81%). Our STRING analysis found that each of these five proteins had more predicted interactions then expected (p-value < 1.0 × 10-16). Our analysis demonstrates that the mutations linked to CM likely affected IDPRs and possibly altered their highly complex PPIs. Quantifying IDPRs in BRAF, NRAS, c-KIT, NF1, and PTEN and understanding these protein regions are important processes as IDPRs can be possible drug targets for novel targeted therapies for treating CM.

Enhanced plasma miR-142-5p promotes the progression of intrahepatic cholangiocarcinoma via targeting PTEN.

The aim of the present study was to evaluate the expression and specific role of microRNA (miR)-142-5p in the progression of intrahepatic cholangiocarcinoma (ICC). Reverse transcription-quantitative polymerase chain reaction was performed to evaluate miR-142-5p expression in patients with ICC and healthy control subjects. The results revealed that plasma miR-142-5p was significantly increased in patients with ICC compared with the control group. Furthermore, miR-142-5p was also increased in ICC tissues compared with adjacent non-neoplastic tissues. Compared with patients with Ta-T1 stage ICC, miR-142-5p was significantly elevated in patients with ICC ≥T2 stage. Patients with ICC at G3 stage had much higher plasma miR-142-5p levels compared with those at G1/2 stage. Receiver operating characteristic analysis indicated that miR-142-5p could be used as a biomarker to differentiate patients with ICC from healthy controls. Kaplan-Meier analysis demonstrated that plasma miR-142-5p was negatively correlated with survival in patients with ICC. A dual luciferase reporter assay indicated that miR-142-5p significantly suppressed the relative luciferase activity of pmirGLO-PTEN-3' untranslated region compared with the control group. In summary, the results of the present study provide novel data indicating that plasma miR-142-5p is significantly upregulated in patients with ICC. miR-142-5p may therefore have potential as a biomarker for screening patients with ICC from healthy controls.

Basal cell carcinoma of the prostate is an aggressive tumor with frequent loss of PTEN expression and overexpression of EGFR.

Basal cell carcinoma (also referred to as adenoid cystic carcinoma) is a rare tumor of the prostate. Although largely characterized as indolent, poor outcomes have been reported in a considerable fraction of cases. As yet, optimum treatment strategies for this cancer have not been developed. This study investigates protein expression of common or potential molecular therapeutic targets and reports on the clinicopathological features of 9 new cases. We evaluated the expression of ERBB2, KIT, androgen receptor, PTEN, EGFR, ERG, and p53 via immunohistochemistry. We also examined EGFR amplification and TMPRSS2-ERG gene rearrangement by fluorescence in situ hybridization. The mean clinical follow-up was 44 months. We found that basal cell carcinoma behaved aggressively with almost one-half of the cases displaying high-risk pathologic features or local recurrence (44%). One patient died as a result of metastatic disease. The most consistent abnormalities included a loss of PTEN expression (56% of cases) and EGFR overexpression (67% of cases). EGFR overexpression occurred in the absence of gene amplification. The TMPRSS2-ERG rearrangement was not detected in any of the tumors studied, nor was ERG protein positivity identified by immunostaining. In addition, ERBB2, KIT, p53, and androgen receptor expressions were either absent or showed only weak, limited reactivity. Our results suggest that there is a high morbidity associated with this tumor, and more intense follow-up and additional treatment may be indicated. Furthermore, targeted therapies directed against the EGFR and PTEN proteins or their constitutive pathways may be promising for future clinical management.