Bone Marrow Mesenchymal Stem Cell (BMSC)-Exosomes Overexpressing miR-141 Inhibit the Malignant Biological Behavior of Glioma Cells via Wnt Signaling

Our study explores whether BMSC-exosomes overexpressing miR-141 can regulate Wnt signal to inhibit the malignant biological behavior of glioma cells. Thirty healthy mice were selected to construct a glioma mouse model and assigned randomly into the control group, miR-141 NC group, and miR-141 mimic group followed by analysis of cell proliferation, apoptosis, protein expression and mRNA expression by MTT method, flow cytometry, Western blot and RT-PCR methods. Compared with the other two groups, miR-141 mimic group showed reduced number of cell proliferation at 24 h and 48 h, decreased cell migration and invasion ability, and the increased cell apoptosis rate (P < 0.05). In miR-141 mimic group, the protein expression of miR-141 was the highest, while the protein expression of β-catenin, survivin and c-myc was the lowest (P < 0.05). In conclusion, BMSC-exosomes overexpressing miR-141 can inhibit the malignant biological behavior of GC cells possibly by inhibiting the activation of Wnt signaling pathway.

miR-12 Derived from Bone Marrow Mesenchymal Stem Cells Accelerates the Development of Human Papillomavirus by Up-Regulating AN1

The miRNA derived from Bone marrow mesenchymal stem cells (BMSCs) have crucial effects on tumors. The tumor could be affected by the abnormal expression of miRNA in human papillomavirus (HPV). Our study aimed to identify the potential brand-new biomarker in order to reveal the pathogenesis of HPV. miRNA derived from BMSCs was detected and identified. The action of miR-12 on biological behavior of HPV was detected. The level of AN1 protein was detected by Western-blot and IHC method. The relationship between miR-12 and AN1 was assessed by bioinformatics analysis and luciferase assay. The tumor cell biological behaviors were evaluated by manipulating miR12 and AN1 level. The tumor volume derived from BMSCs was diminished significantly compared with normal tissues. The tumor volume was bigger after combined injection with Hela cell and miR-12 compared with single injection. The cell proliferative and invasive ability was strengthened after transfection with miR-12mimics. The cell invasive ability was reduced significantly after transfection of si-miR-12. AN1 was a target gene of miR-12 as confirmed by the analysis on bioinformatics and luciferase activity. The phenotype was reversed after the silent presentation of AN1 was disturbed. In conclusion, miR-12 expression is elevated in HPV cells and affects HPV cells through targeting the AN1 signaling pathway.

The Mechanism of Human Umbilical Mesenchymal Stem Cells (HUMSC) on Biological Behavior of Human Papillomavirus (HPV) Cells Through Restraining the Programmed Cell Death Protein 1/Programmed Cell Death Ligand 1 (PD-1/PD-L1) Signal Pathway

Biological behavior of HPV cell was observed by HUMSC through restraining PD-1/PD-L1 signal pathway. And HUMSC was adopted as target cell for the treatment on HPV. The rat HPV model was established and divided into three groups including blank group, control group and test group according to different reagents being injected into rats. Use HE staining method to observe the cancerous transformation of tumor tissue sections. The gene presentation of PD-1/PD-L1 and lymphocyte was detected with Western blot. The invasion and migration condition of cancer cells was observed from experiment in vitro. The quantity of cancer cells in test group was the least. And invasion and migration ability in test group was the weakest. The control group was the second. The number of tumor cells in the blank group was the largest. Strongest ability to invade and migrate. The presentation of PD-L1 was restrained partly by HUMSC. The increasing of immune-associated cells could be prompted by HUMSC. The quantity of CD3+, CD4+ and CD8+ in PB was the most in test group. The expression of blank groups is the lowest than others restrained by HUMSC. And quantity of abundant immune cells including CD3+, CD4+ and CD8+ could be activated partly through activating immune action of body. And monitoring function of immune system on HPV cells could be increased effectively. The invasion and migration ability in vitro of HPV could be reduced partly.

The functions and prognostic value of Krüppel‐like factors in breast cancer

Background Krüppel‐like factors (KLFs) are zinc finger proteins which participate in transcriptional gene regulation. Although increasing evidence indicate that KLFs are involved in carcinogenesis and progression, its clinical significance and biological function in breast cancer are still limited. Methods We investigated all the expression of KLFs (KLF1-18) at transcriptional levels by using Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA). The mRNA and protein expression levels of KLFs were also determined by using RT-qPCR and immunohistochemistry, respectively. CBioPortal, GeneMANIA and STRING were used to comprehensive analysis of the molecular characteristics of KLFs. The clinical value of prognostic prediction based on the expression of KLFs was determined by using the KM plotter. The relevant molecular pathways of KLFs were further analyzed by using Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Finally, we investigated the effect of KLF2 and KLF15 on biological behavior of breast cancer cells in vitro. Results The expression of KLF2/4/6/8/9/11/15 was significantly down-regulated in breast cancer. The patients with high KLF2, KLF4 or KLF15 expression had a better outcome, while patients with high KLF8 or KLF11 had a poor prognosis. Furthermore, our results showed that KLF2 or KLF15 can be used as a prognostic factor independent on the other KLFs in patients with breast cancer. Overexpression of KLF2 or KLF15 inhibited cell proliferation and migration, and blocked cell cycle at G0/G1 phase, resulting in cell apoptosis. Conclusions KLF2 and KLF15 function as tumor suppressors in breast cancer and are potential biomarkers for prognostic prediction in patients with breast cancer.

Midface Resection And Reconstruction In Head And Neck Oncology: A 20 Years Single Institution Experience

Background: Midface tumors are relatively uncommon as midface comprises less than 1% of all malignant tumors and incorporate a distinct group of lesions, with a high variety of histological types and biological behavior. The purpose of the study is to present our experience in managing patients with advanced midface tumors for a 20-year period.Materials & Methods: From January 2000 to May 2020, we performed 72 excisions and reconstructions in 36 patients where their medical records were reviewed by the head and neck oncology clinic. The commonest anatomical site of the primary was the maxilla in 19 patients and bilaterally in 5 patients. In 15 patients there was an orbital and anterior fossa extension. In 6 patients there was a parotid and middle ear extension and in 1 patient there was a lip involvement.Results: Surgical resection included maxillectomy in the majority of the cases in combination with orbital exenteration or orbitectomy and anterior fossa resection. In 8 cases parotidectomy and mastoidectomy/ core petrosectomy was performed. One patient was subjected to total petrosectomy. Reconstruction was performed with radial forearm osteocutaneous free flap in 4 cases, latissimus with scapular bone flap in one case, lengthening temporalis myoplasty in 19 cases, rectus femoris in one case and anterolateral thigh flap in 5 cases in combination with temporalis and vastus lateralis in one case respectively and bilateral karapandzic flap in 1 case. The patients were followed-up from 2005 to 2020. To date, 23 patients (63.8%) are disease free with no recurrences of the disease and 4.4% of all patients presented disease recurrence during the follow-up period.Conclusions: In conclusion midface resections are safely performed with a combination of microvascular and dynamic reconstruction of the face offering our patients quality of life improvement.Level of Evidence: Level V, therapeutic study

Liver Transplantation for Hepatocellular Carcinoma: How Should We Improve the Thresholds?

Hepatocellular carcinoma (HCC) is the third highest cause of cancer-related mortality, and liver transplantation is the ideal treatment for this disease. The Milan criteria provided the opportunity for HCC patients to undergo LT with favorable outcomes and have been the international gold standard and benchmark. With the accumulation of data, however, the Milan criteria are not regarded as too restrictive. After the implementation of the Milan criteria, many extended criteria have been proposed, which increases the limitations regarding the morphological tumor burden, and incorporates the tumor’s biological behavior using surrogate markers. The paradigm for the patient selection for LT appears to be shifting from morphologic criteria to a combination of biologic, histologic, and morphologic criteria, and to the establishment of a model for predicting post-transplant recurrence and outcomes. This review article aims to characterize the various patient selection criteria for LT, with reference to several surrogate markers for the biological behavior of HCC (e.g., AFP, PIVKA-II, NLR, 18F-FDG PET/CT, liquid biopsy), and the response to locoregional therapy. Furthermore, the allocation rules in each country and the present evidence on the role of down-staging large tumors are addressed.

Comprehensive Assessment of Serum hsa_circ_0070354 as a Novel Diagnostic and Predictive Biomarker in Non-small Cell Lung Cancer

Background: More and more studies have shown that circular RNAs (circRNAs) play an essential role in the occurrence and development of tumors. Hence, they can be used as biomarkers to assist in diagnosing tumors. This study focuses on exploring the role of circular RNA (hsa_circ_0070354) in the diagnosis and prognosis of non-small cell lung cancer (NSCLC).Materials and Methods: First of all, high-throughput sequencing was used to find the difference in the expression of circular RNA between NSCLC and adjacent tissues. The circRNAs with higher differences in expression were selected to verify their expressions in tissues, cells, and serum using qRT-PCR. Secondly, the hsa_circ_0070354 with a significant difference was chosen as the research goal, and the molecular properties were verified by agarose gel electrophoresis and Sanger sequencing, etc. Then, actinomycin D and repeated freeze-thaw were used to explore the stability and repeatability of hsa_circ_0070354. Finally, the expression of hsa_circ_0070354 in serum of 133 patients with NSCLC and 97 normal donors was detected, and its sensitivity, specificity, and prognosis as tumor markers were statistically analyzed.Results: Hsa_circ_0070354 was highly expressed in tissues, cells, and serum of NSCLC, and it has the characteristics of sensitivity, stability, and repeatability. The ROC curve indicates that hsa_circ_0070354 is superior to conventional tumor markers in detecting NSCLC, and the combined diagnosis is of more significance in the diagnosis. The high expression of hsa_circ_0070354 is closely related to the late-stage, poor differentiation of the tumor and the short survival time of the patients, which is an independent indicator of poor prognosis.Conclusion: Hsa_circ_0070354 is not only a novel sensitive index for the diagnosis of NSCLC but also a crucial marker for bad biological behavior.

Relationship Between Clustered Ring Nonmass Enhancement of Breast MRI and Prognostic Molecular Biomarkers in Breast Cancer

BackgroundClustered ring enhancement (CRE) of breast MRI is a lexicon of nonmass enhancement (NME) representing tendency of breast cancer and molecular biomarkers are predictors of response to therapy. The purpose of this study was to retrospectively determine the relationship between CRE NME and prognostic molecular biomarkers in breast cancer.MethodsRetrospective analysis of 58 breast lesions in 56 female patients between July 2013 and December 2018 was performed in our institution. Cases with MRI reporting NME in the text were collected via searching the report database. The patterns of enhancement including CRE on breast MRI were reviewed by a radiologist blinded to pathology report. The pathological results and expression of molecular biomarkers were collected. Univariate analysis was applied to evaluate the association between MRI NME imaging features, pathological and IHC stain findings.Results58 Breast lesions were pathologically proven breast carcinoma, and 31 lesions with CRE and 27 lesions without CRE on breast MRI. The expression of estrogen receptor (ER) (P=0.017) and progesterone receptor (PR) (P=0.017) was significantly lower in lesions with CRE compared with those without CRE. The expression of Ki-67 (≥ 25%) was significantly higher in lesions with CRE(P=0.046). The lesions with CRE have a lower expression ratio of ER (50.71 ± 45.39% vs. 74.26 ± 33.59%, p= 0.028).ConclusionOur results indicated that lesions with CRE may possess different features from those without CRE in molecular expression. They tend to bear a more aggressive biological behavior.

The Role of Cyclodextrins in the Design and Development of Triterpene-Based Therapeutic Agents

Triterpenic compounds stand as a widely investigated class of natural compounds due to their remarkable therapeutic potential. However, their use is currently being hampered by their low solubility and, subsequently, bioavailability. In order to overcome this drawback and increase the therapeutic use of triterpenes, cyclodextrins have been introduced as water solubility enhancers; cyclodextrins are starch derivatives that possess hydrophobic internal cavities that can incorporate lipophilic molecules and exterior surfaces that can be subjected to various derivatizations in order to improve their biological behavior. This review aims to summarize the most recent achievements in terms of triterpene:cyclodextrin inclusion complexes and bioconjugates, emphasizing their practical applications including the development of new isolation and bioproduction protocols, the elucidation of their underlying mechanism of action, the optimization of triterpenes’ therapeutic effects and the development of new topical formulations.

Heat Treatment Effect on Biological Behavior of Polyetheretherketone Composites

Polyetheretherketone is a semi-crystalline thermoplastic polymer, that so with heat treatments, it is possible to get different properties which are very important for the material performance. Heat treatment is a broadly utilized to develop the semi-crystalline polymers properties. In the present investigation, annealing of polyetheretherketone (PEEK) was carried out at temperatures above its glass transition temperature (Tg) to study its effects upon the biological conduct of the control and PEEK ternary composites. The bioactivity of the specimens was evaluated by investigating the apatite formation after immersion for different periods in a simulated body fluid (SBF). The biocompatibility of specimens was assessed by MTT assay. Additionally, the antibacterial property of the specimens versus S. aureus was observed with the optical density methods. The results manifested that the formation of hydroxyapatite was obviously observed on specimens after immersion for (7 and 14 days) in the simulated body fluid (SBF). Otherwise, the results of MTT assay recorded the PEEK specimens that excited the activity of fibroblasts, and therefore a high cytocompatibility was noticed and the specimens revealed antibacterial properties against S. aureus. So, the results of the bioactivity, biocompatibility and antibacterial tests in vitro demonstrated that the heat treatment enhanced biological behavior.