Integrative Nomogram of Computed Tomography Radiomics, Clinical, and Tumor Immune Features for Analysis of Disease-Free Survival of NSCLC Patients with Surgery.

To improve prognosis of cancer patients and determine the integrative value for analysis of disease-free survival prediction, a clinic investigation was performed involving with 146 non-small cell lung cancer (NSCLC) patients (83 men and 73 women; mean age: 60.24 years ± 8.637) with a history of surgery. Their computed tomography (CT) radiomics, clinical records, and tumor immune features were firstly obtained and analyzed in this study. Histology and immunohistochemistry were also performed to establish a multimodal nomogram through the fitting model and cross-validation. Finally, Z test and decision curve analysis (DCA) were performed to evaluate and compare the accuracy and difference of each model. In all, seven radiomics features were selected to construct the radiomics score model. The clinicopathological and immunological factors model, including T stage, N stage, microvascular invasion, smoking quantity, family history of cancer, and immunophenotyping. The C-index of the comprehensive nomogram model on the training set and test set was 0.8766 and 0.8426 respectively, which was better than that of the clinicopathological-radiomics model (Z test, P =0.041<0.05), radiomics model and clinicopathological model (Z test, P =0.013<0.05 and P =0.0097<0.05). Integrative nomogram based on computed tomography radiomics, clinical and immunophenotyping can be served as effective imaging biomarker to predict DFS of hepatocellular carcinoma after surgical resection.

Retracted: Overexpression of Neuregulin-1 (NRG-1) Gene Contributes to Surgical Repair of Brachial Plexus Injury After Contralateral C7 Nerve Root Transfer in Rats.

Retracted on the author's request: "We would like to withdraw our manuscript. We restarted the project for further study last year, we found that the results in this study are not solid enough and need to be further explored." Reference: Zong-Qiang Wang, Dian-Hui Xiu, Gui-Feng Liu, Jin-Lan Jiang. Overexpression of Neuregulin-1 (NRG-1) Gene Contributes to Surgical Repair of Brachial Plexus Injury After Contralateral C7 Nerve Root Transfer in Rats. Med Sci Monit 2018; 24: 5779-5787; DOI: 10.12659/MSM.908144.

Long non-coding RNA XIST binding to let-7c-5p contributes to rheumatoid arthritis through its effects on proliferation and differentiation of osteoblasts via regulation of STAT3.

BACKGROUND: Rheumatoid arthritis (RA), a chronic autoimmune disease, affects around 1% population worldwide, with the life quality of patients severely reduced. In this study, it is intended to explore the role of long non-coding RNA X-inactive specific transcript (lncRNA XIST) in RA and the underlying mechanisms associated with let-7c-5p and signal transducer and activator of transcription 3 (STAT3). METHODS: LncRNA XIST, let-7c-5p, and STAT3 expressions were determined in RA and normal cartilage tissues, and their relationship was analyzed in osteoblasts. The regulatory effects of lncRNA XIST in RA were investigated when XIST expression was upregulated or downregulated in osteoblasts. TNF-α, IL-2, IL-6, alkaline phosphatase (ALP), osteocalcin, TGF-ß1, and IGF1 were measured in vivo in RA rats. RESULTS: LncRNA XIST and STAT3 were expressed at high levels and let-7c-5p expressed at a low level in RA cartilage tissues. LncRNA XIST silencing or let-7c-5p enhancement led to decreased levels of TNF-α, IL-2, and IL-6, suggestive of suppressed inflammatory response, and increased levels of ALP, osteocalcin, TGF-ß1, and IGF-1 as well as reduced damage in cartilage tissues. CONCLUSION: LncRNA XIST downregulation could promote proliferation and differentiation of osteoblasts in RA, serving as a future therapeutic target for RA.

Knockdown of lncRNA TUG1 Enhances Radiosensitivity of Prostate Cancer via the TUG1/miR-139-5p/SMC1A Axis.

BACKGROUND: Prostate cancer (PCa) is a common malignant tumor of the urinary system in males. LncRNA taurine-upregulated gene 1 (TUG1) has been verified to play a crucial role in progression and prognosis of PCa. However, the functional mechanism of TUG1 remains unclear with radiosensitivity of PCa. METHODS: Quantitative real-time PCR (qRT-PCR) was conducted to measure the transcription levels of genes. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis were employed to assess cell proliferation and apoptosis, respectively. Moreover, colony formation assay was used to measure colony survival. Western blot was performed to detect the relative proteins expression. The interaction among variables was predicted by online tool starbase, and then confirmed using the dual luciferase reporter assay. A xenograft mouse model was constructed to investigate the effect of TUG1 on tumor growth in vivo. RESULTS: The levels of lncRNA TUG1 and SMC1A were remarkably increased, while miR-139-5p was downregulated in PCa. Patients with high expression of TUG1 showed a lower survival rate and poor prognosis. Knockdown of TUG1 inhibited PCa cell proliferation and colony survival fraction, and promoted apoptosis. Downregulation of miR-139-5p reversed the effects of TUG1 deletion on proliferation, apoptosis and colony survival fraction in PCa cells treated with 4 Gy of X-ray radiation. Moreover, TUG1 sponged miR-139-5p to regulate SMC1A expression. SMC1A deletion blocked the effects of TUG1 on the progression of PCa cells treated with 4 Gy of X-ray radiation. The tumor volume and weight were illustriously reduced with radiation and TUG1 silencing in xenograft model. CONCLUSION: Knockdown of lncRNA TUG1 enhanced radiosensitivity in PCa via the TUG1/miR-139-5p/SMC1A axis. It may become a promising target for PCa treatment.

miR-129-5p inhibits prostate cancer proliferation via targeting ETV1.

BACKGROUND: Prostate cancer is one of the most commonly diagnosed diseases in males. METHODS: RT-qPCR was used to detect miR-129-5p expression in tumor tissues and adjacent normal tissues from patients with prostate cancer. The cell proliferation assay and colony forming assay were used to study the role of miR-129-5p in mediating prostate cancer cell growth. Bioinformatic analysis and dual luciferase assay were performed to predict and confirm ETV1 as a target gene of miR-129-5p. RESULTS: We found that miR-129-5p levels were decreased significantly in human prostate cancer tissues compared with matched normal tissues from patients with prostate cancer. Overexpression of miR-129-5p suppressed prostate cancer cell growth while antagonist of miR-129-5p promoted cell proliferation in immortal prostate cell line RWPE-1. In addition, elevation of miR-129-5p decreased ETV1 expression in prostate cancer cells while downregulation of miR-129-5p increased ETV1 expression in RWPE-1. Mechanistically, ETV1 is confirmed a direct target of miR-129-5p in prostate cancer cells. Through repression of ETV1 expression, miR-129-5p could inactivate YAP signaling in prostate cancer cells. In addition, overexpression of ETV1 attenuated miR-129-5p induced cell proliferation in prostate cancer cells. Correlation analysis further revealed that there was a negative correlation between miR-129-5p levels and ETV1 mRNA levels in tumor tissues from patients with prostate cancer. CONCLUSION: Our results identified miR-129-5p as a tumor suppressor in prostate cancer via repression of ETV1.

Long non-coding RNA LINC00968 attenuates drug resistance of breast cancer cells through inhibiting the Wnt2/ß-catenin signaling pathway by regulating WNT2.

BACKGROUND: Breast cancer is one the most common cancers, making it the second leading cause of cancer-related death among women. Long non-coding RNAs (lncRNAs), with tightly regulated expression patterns, also serve as tumor suppressor during tumorigenesis. The present study aimed to elucidate the role of LINC00968 in breast cancer via WNT2-mediated Wnt2/ß-catenin signaling pathway. METHODS: Breast cancer chip GSE26910 was utilized to identify differential expression in LINC00968 and WNT2. The possible relationship among LINC00968, transcriptional repressor HEY and WNT2 was analyzed and then verified. Effects of LINC00968 on activation of the Wnt2/ß-catenin signaling pathway was also tested. Drug resistance, colony formation, cell migration, invasion ability and cell apoptosis after transfection were also determined. Furthermore, tumor xenograft in nude mice was performed to test tumor growth and weight in vivo. RESULTS: WNT2 expression exhibited at a high level, whereas LINC00968 at a low expression in breast cancer which was also associated with poor prognosis in patients. LINC00968 targeted and negatively regulated WNT2 potentially via HEY1. Either overexpressed LINC00968 or silenced inhibited activation of the Wnt2/ß-catenin signaling pathway, thereby reducing drug resistance, decreasing colony formation ability, as well as suppressing migration and invasion abilities of breast cancer cells in addition to inducing apoptosis. Lastly, in vivo experiment suggested that LINC00968 overexpression also suppressed transplanted tumor growth in nude mice. CONCLUSION: Collectively, overexpressed LINC00968 contributes to reduced drug resistance in breast cancer cells by inhibiting the activation of the Wnt2/ß-catenin signaling pathway through silencing WNT2. This study offers a new target for the development of breast cancer treatment.

MicroRNA-543 suppresses liver cancer growth and induces apoptosis via the JAK2/STAT3 signaling pathway.

The aim of the present study was to investigate the function of microRNA-543 on liver cancer cell proliferation and apoptosis, and also to identify whether the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway was a direct target of microRNA-543. When compared with paracarcinoma tissue, microRNA-543 expression in tissue samples from patients with liver cancer was identified to be decreased. Furthermore, overall survival of patients with high microRNA-543 expression was increased compared with patients with low microRNA-543 expression. Inhibition of microRNA-543 expression increased cell proliferation and decreased apoptosis of liver cancer cells. It also activated the protein expression of phosphorylated JAK2, phosphorylated STAT3, c-Myc and B-cell lymphoma 2 (Bcl-2) in liver cancer cells. However, activation of microRNA-543 expression in turn decreased cell proliferation and increased apoptosis of liver cancer cells. The results of the present study highlight the pivotal function of microRNA-543 as an inhibitor in liver cancer cell proliferation by observing JAK2/STAT3/c-Myc/Bcl-2 in liver cancer.

Comprehensive analysis of marker gene detection and computed tomography for the diagnosis of human lung cancer.

Non-small cell lung cancer (NSCLC) is one of leading causes of cancer-associated mortality, with a high number of cases caused by metastasis. The early diagnosis of cancer contributes to the successful treatment of patients with lung cancer. The aim of the present study was to analyze the efficacy of marker gene detection and computed tomography (CT) in diagnosing human lung cancer. Lung cancer marker genes, including carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), tissue polypeptide antigen (TPA), pro-gastrin-releasing peptide (ProGRB), cytokeratin fragment 21-1 (Cyfra21-1) and neuron-specific enolase (NSE), were analyzed in patients with lung cancer. The tumor size was evaluated using CT, and the association between lung serum levels of marker gene protein expression and tumor size was investigated. A total of 328 patients with lung cancer were identified, including 204 adenocarcinoma, 75 large cell carcinoma and 49 squamous cell carcinoma cases. All patients were indicated to have a high serum level of CEA, CA125, TPA, ProGRB, Cyfra21-1 and NSE, compared with the normal range. Immunohistochemistry demonstrated higher expression levels of CEA, CA125, TPA, ProGRB, Cyfra21-1 and NSE in lung tumor tissues, compared with the normal range. Results indicated that CT was able to diagnose tumor size for patients with lung cancer. The CEA and CA125 expression levels were associated with CT-diagnosed adenocarcinoma tumor size. Large cell carcinoma tumor size was associated with serum levels of CEA, TPA and ProGRB. Results indicated that Cyfra21-1 and NSE were associated with the squamous cell carcinoma cases, as demonstrated using CT. In conclusion, these results indicated that comprehensive analysis of marker gene detection and CT results may be used to diagnose human lung cancer.

Overexpression of Neuregulin-1 (NRG-1) Gene Contributes to Surgical Repair of Brachial Plexus Injury After Contralateral C7 Nerve Root Transfer in Rats.

BACKGROUND Surgeons usually transfer the contralateral C7 to the median nerve on the injured side via a nerve graft to recover sensation and movement in a paralyzed hand. The purpose of our study was to determine whether NRG-1 affects the recovery of nerve function in brachial plexus injury after contralateral C7 nerve root transfer in a rat model. MATERIAL AND METHODS An injury model of left brachial plexus and contralateral C7 nerve root transfer was established. Four weeks after the operation, NRG-1 expression was examined by reverse transcription quantitative polymerase chain reaction and Western blot analysis. The diameter rate differences of the healthy limb and affected limb were estimated. The postoperative mass of the left latissimus dorsi, triceps, extensor carpi radialis brevis, and musculus extensor digitorum were examined. The number of nerve fibers and typical area of the affected side were assessed. Postoperative left motor nerve conduction velocity (MNCV) and motor nerve action potential (MNAP) were tested by use of a biological information recording and collecting system. RESULTS Eukaryotic expression plasmid of pcDNA4/myc/A-NRG-1 was successfully constructed, and NRG-1 was overexpressed. Compared with the model group, the NRG-1 group had a lower rate of differences of the limbs; higher mass of left latissimus dorsi, triceps, extensor carpi radialis brevis, and musculus extensor digitorum; more nerve fibers and larger typical area in the affected side, left MNCV, and MNAP; and wider CSA of the left triceps. CONCLUSIONS These results demonstrated that NRG-1 can promote recovery of nerve function in brachial plexus injury after contralateral C7 nerve root transfer in rats.

Sumoylation of SMAD 4 ameliorates the oxidative stress-induced apoptosis in osteoblasts.

Oxidative stress-induced mitochondrial function and cell apoptosis to osteoblasts, plays a critical role in the pathophysiology of osteoporosis. However, mechanisms underlying such process remain not yet clear. We aims in this study to investigate a possible role of SMAD (the mothers against decapentaplegic homolog 4 (SMAD4) in the oxidative stress-induced apoptosis, in homo sapiens osteoblast hFOB1.19 cells. Results demonstrated that the treatment with more than 100µM H2O2 significantly downregulated the cellular viability, whereas markedly induced apoptosis in hFOB1.19 cells. The SMAD4 was markedly reduced in both mRNA and protein levels in the H2O2 -treated hFOB1.19 cells, along with the reduction of Small ubiquitin-related modifier 1 (SUMO 1) and SUMO 2/3. The immunoprecipitation assay confirmed indicated the interaction between SUMO 1 (or SUMO 2/3) and SMAD4. Moreover, the SMAD4 overexpression markedly ameliorated the H2O2-resulted viability reduction and apoptosis induction in hFOB1.19 cells. Interestingly, such amelioration was blocked by the knockdown of SUMO 2/3. Taken together, we conclued that SMAD4 inhibits the H2O2-induced apoptosis in osteoblast hFOB1.19 cells; such inhibition might depend on the SUMOylation by SUMO 2/3. It implies a promising role of SMAD4 in oxidative stress-promoted damage to osteoblasts.

Annexin A2 Coordinates STAT3 to Regulate the Invasion and Migration of Colorectal Cancer Cells In Vitro.

The present study aimed to reveal the expression of STAT3 and Anxa 2 in CRC specimens and to investigate the effects of STAT3 and Anxa 2 signaling on the proliferation, invasion, and migration in CRC Caco-2 cells. Results demonstrated that both Anxa 2 and STAT3 were highly expressed in CRC specimens in both mRNA and protein levels, with or without phosphorylation (Tyrosine 23 in Anxa 2 and Tyrosine 705 in STAT3). And the upregulated Anxa 2 promoted the phosphorylation of STAT3 (Tyrosine 705) in CRC Caco-2 cells. The upregulated Anxa 2 promoted the proliferation, migration, and invasion of Caco-2 cells in vitro. Moreover, the STAT3 knockdown also repressed the proliferation, migration, and invasion of Caco-2 cells. In conclusion, the overexpressed Annexin A2 regulated the proliferation, invasion, and migration in CRC cells in an association with STAT3.

Application of MSCTA combined with VRT in the operation of cervical dumbbell tumors.

Cervical dumbbell tumor poses great difficulties for neurosurgical treatment and incurs remarkable local recurrence rate as the formidable problem for neurosurgery. However, as the routine preoperative evaluation scheme, MRI and CT failed to reveal the mutual three-dimensional relationships between tumor and adjacent structures. Here, we report the clinical application of MSCTA and VRT in three-dimensional reconstruction of cervical dumbbell tumors. From January 2012 to July 2014, 24 patients diagnosed with cervical dumbbell tumor were retrospectively analyzed. All patients enrolled were indicated for preoperative MSCTA/VRT image reconstruction to explore the three-dimensional stereoscopic anatomical relationships among neuroma, spinal cord and vertebral artery to achieve optimal surgical approach from multiple configurations and surgical practice. Three-dimensional mutual anatomical relationships among tumor, adjacent vessels and vertebrae were vividly reconstructed by MSCTA/VRT in all patients in accordance with intraoperative findings. Multiple configurations for optimal surgical approach contribute to total resection of tumor, minimal damage to vessels and nerves, and maximal maintenance of cervical spine stability. Preoperative MSCTA/VRT contributes to reconstruction of three-dimensional stereoscopic anatomical relationships between cervical dumbbell tumor and adjacent structures for optimal surgical approach by multiple configurations and reduction of intraoperative damages and postoperative complications.

The differences in imaging features of malignant and benign branch duct type of Intraductal Papillary Mucinous Tumor.

OBJECTIVE: To investigate the difference in the radiological features of malignant and benign branch duct type of IPMT (Intraductal Papillary Mucinous Tumor) of the pancreas. METHODS: Thirty-six patients who were referred for operation with branch duct type of IPMT of the pancreas were included in this study. All cases underwent both CT and MRI with contrast enhancement. The size of the cystic lesions, the presence and size of mural nodules, and the amount of dilatation of the MPD were assessed by two independent radiologists, and the results were compared with pathological findings. RESULTS: Histological examination revealed adenoma in 8 cases, AH (atypical hyperplasia) in 8 cases, CIS (carcinoma in situ) in 8 cases and invasive carcinoma in 12 cases. Patients of the malignant group were older than those in the benign group (mean age: 67 yrs vs 60 yrs, respectively), but no statistically significant (p=0.05). Males (16/4 vs 10/6) more often complained weight loss and jaundice. The malignant tumor was more frequently located in the head-body and body. Compared with the benign group, the mean sizes of the cyst, mural nodules, MPD of the malignant group were 44 mm, 13 mm, 7.5 mm and benign group were 31 mm, 5 mm, 3.5 mm respectively. All these difference are statistically significant (p<0.05). In 4 cases of the 20 in the malignant group, soft tissue suggesting spread of disease into the adjacent viscera and peritoneum was detected. CONCLUSION: Cyst size over 30 mm and mural nodule over 8 mm, irregular thick septa, dilatation of the MPD, and accompany with soft tissue mass may be helpful factors in determining malignancy.

In vivo photodynamic therapy and magnetic resonance imaging of cancer by TSPP-coated Fe3O4 nanoconjugates.

In this paper, we present the preparation and characterization of organic dye-coated magnetic particles and its application as magnetic resonance imaging (MRI) and photodynamic therapy (PDT) agent. We have coated the surface of Fe3O4 magnetic nanoparticles by meso-tetra(4-sulfonatophenyl) porphyrin dihydrochloride (TSPP), a photosensitive drug used in PDT, which is capable of generating singlet oxygen on the surface of paramagnetic Fe3O4 nanoparticles when irradiated at 400 nm. While the MRI was performed with in vivo mice experiment along with proper irradiation and therapeutic effect was followed by using in-situ MRI technology. The resulting conjugate is a single particle platform that can simultaneously be used as a PDT therapeutic and MRI contrasting agent.