Search

Background Anoikis resistance plays a critical role in the tumor metastasis by allowing survival of cancer cells in the systemic circulation. We previously showed that long non-coding RNAs APOC1P1-3 (lncRNA APOC1P1-3) inhibit apoptosis of breast cancer cells. In this study, we explored its role in anoikis resistance. Methods We induced anoikis resistance in two breast cancer cell lines (MCF-7 and MDA-MB-231) under anchorage-independent culture conditions and studied lncRNA APOC1P1-3 effects on apoptosis. Using Dual-Luciferase activity assay, we determined whether it specifically binds to miRNA-188-3P. We further explored its role in lung metastasis by injecting MDA-MB-231 and MDA-MB-231-APOC1P1-3-knock-down cells in female BALB/c nude mice. Results We found that lncRNA APOC1P1-3 suppressed early apoptosis of these cells (demonstrated by gain or loss of their function, respectively) and promoted anoikis resistance via reducing activated- Caspase 3, 8, 9 and PARP. Moreover, it specifically binds to the target miRNA-188-3p acting as a “sponge” to block the inhibition of Bcl-2 (an anti-apoptosis protein). Conclusions Our study supports a theory that lncRNA APOC1P1-3 can promote development of breast cancer metastasis via anoikis resistance by specifically binding to miRNA-188-3p to block the inhibition of Bcl-2.

Background Fibular flaps have been widely used for mandibular and maxillary reconstructions. On occasion, anatomical variants of fibular arteries (FA) will be encountered. Purpose Although anatomical variants of FA during fibular harvest have been reported, controversy exists regarding whether simple color Doppler ultrasonography (CDU) and physical examinations (PE) are sufficient for early preoperative detection. Material and Methods A 10-year retrospective analysis in our department was performed to find the patients with various FA anomalies confirmed by computed tomography angiography (CTA) or intraoperative findings. Results A total number of 19 FA anomalies were found either pre- or intraoperatively in 16 patients, in whom three cases were with bilateral FA variants. Type IIIC variants, also called arteria peronea magna (great peroneal artery), were confirmed in two legs, while the majority (13 legs) had type IIIA hypoplastic/aplastic posterior tibialis arteries (PTA). Four legs had new type IIID (low FA and PTA bifurcations). Preoperative CDU and PE only suspected anomalies in two legs. Six cases proceeded with using the affected fibulas, within whom vascular grafts were used in half of them for lengthening the FA pedicle. Local ischemia, partial soleus muscle necrosis, and claudication were reported in one. Conclusions Routine CTA before every fibular harvest, rather than simple PE and CDU, should be added for screening contraindications and ensuring safety for fibular flap harvest.

Objectives Basal cell carcinoma is the most common skin cancer worldwide. Surgical excision is considered as the mainstay of treatment, while the evidence of excision margin in advanced stage is lacking, especially in maxillofacial area. Materials and methods We conducted a 2-center retrospective cohort study. Disease-free survival rate was estimated for 116 Asian patients with T3 basal cell carcinoma in maxillofacial area who received stand surgical excision with margin of 3-5 mm (Group A), 6-9 mm (Group B), and 10-15 mm (Group C). Results For the entire cohort, five-year disease-free survival rates of Groups A, B, and C were 82.1%, 93.5%, and 92.4%, respectively. When compared with Group B, Group A was correlated with lower disease-free survival rate (HR 5.48, p = .04), and Group C was not associated with different disease-free survival rate (HR 0.85, p = .62). Perineural invasion (p = .006) and pathologic subtypes of infiltrative basal cell carcinoma (p = .01) were independent prognosticator for disease-free survival rate. Conclusions This multicenter cohort study validated that T3 basal cell carcinoma Asian patients of maxillofacial area treated with excision margin of 6-9 mm had a substantial benefit of disease-free survival rate and skin conservation.

Objective To evaluate the differences between two types of decompression for treating large mandibular odontogenic cysts. Materials and methods This retrospective, cohort study included patients who were diagnosed for large mandibular odontogenic cysts from January 2015 to April 2018 and underwent two different types of decompression based on removal or retention of the cyst wall. The primary outcome was the percentage of the residual cyst area within 1 year after surgery. We used the propensity score matching (PSM) to balance the covariates of the two groups, and the primary outcome was analyzed by the non-inferiority test. Results A total of 93 cases were included in our study. After 1 year, the wall removal group was non-inferior to the wall retaining group in terms of cyst area, cyst volume, and the difference between the HU values of the original cyst region and the normal mandible. In subgroup analysis, we found there were no differences between two groups in the percentage of patients in whom the cystic area was reduced by 90% after 1 year. Conclusion Our findings suggest that the wall removal group showed better results than the cyst wall retaining group in large mandibular odontogenic cysts.

Supplemental material, sj-pdf-5-acr-10.1177_0284185120980001 for Standardize routine angiography assessment of leg vasculatures before fibular flap harvest: lessons of congenital and acquired vascular anomalies undetected by color Doppler and physical examinations by Chunyue Ma, Lei Wang, Zhuowei Tian, Xingjun Qin, Dan Zhu, Jinbao Qin and Yi Shen in Acta Radiologica

Additional file 1: Table S1. Verification of the non-coding characteristics of lncRNA-APOC1P1-3. Table S2. Comparison of the target microRNAs with different databases. Table S3. 20 sets of random mutations for binding sites, and its thermodynamics. Table S4. The primer sequences are described in Table S4. Figure S1. Thermodynamic analysis of the predicted binding sites by BiBiServ-RNAhybrid. Figure S2. Site-directed mutation in pmirGLO-APOC1P1-3’UTR plasmid.

Background Anoikis resistance plays a critical role in the tumor metastasis by allowing survival of cancer cells in the systemic circulation. We previously showed that long non-coding RNAs APOC1P1-3 (lncRNA APOC1P1-3) inhibits breast cancer cell apoptosis. However, its role in the anoikis resistance remains unclear. Methods We induced anoikis resistance in two breast cancer cell lines (MCF-7 and MDA-MB-231) under anchorage-independent culture condition and studied the effects of lncRNA APOC1P1-3 on the apoptosis. The Dual-Luciferase activity assay were used to whether miRNA-188-3P can specifically bind to lncRNA APOC1P1-3. We further explored the role of APOC1P1-3 in the lung metastasis by injecting MDA-MB-231 and MDA-MB-231-APOC1P1-3-knock-down cells in the female BALB/c nude mice. Results We found that it suppressed early apoptosis of these cells by gain or loss of their function, respectively. We further explored its mechanism related to anoikis resistance, and found this molecule promoted the resistance via activating Caspase 3, 8, 9 and PARP. Moreover, it was specifically binding to the target miRNA-188-3p to block its inhibition of Bcl-2 (an anti-apoptosis protein). These findings suggest that lncRNA APOC1P1-3 plays an important role in the development of breast cancer metastasis via anoikis resistance. Conclusions This study demonstrates that lncRNA APOC1P1-3 can promote the anoikis resistance of breast cancer cells and specifically bind to miRNA-188-3p acting as a “sponge” to block the inhibition of anti-apoptotic protein Bcl-2.

Pingyangmycin (PYM) has been applied clinically for many years to treat vascular malformations (VM) in China. The major limitation of PYM injections is quick diffusion from the injection site, which increases side effects, especially the possibility of pulmonary injury. In this paper, chitosan/glycerophosphate disodium (CS/GP) thermogels containing liposomes for sustained and localized PYM delivery were prepared and optimized by a three-level three-factorial Box–Behnken experimental design to evaluate the effects of different variables (the PYM concentration, CS amount and GP content), on the selected responses (cumulative percentage PYM released in 1 day, 9 days and the rate constant k). The results revealed that the optimized PYM liposomal thermogels had a controlled PYM release for 14 days in vitro, which confirmed the validity of optimization. In vitro morphological observation, cell cycle and apoptosis analysis showed an effective anti-proliferation action of PYM liposomal thermogels on human vascular endothelial cells (EA.hy926). In vivo pharmacokinetics research in rabbits displayed that compared with PYM liposomes and PYM thermogels, PYM liposomal thermogels had a better controlled delivery of PYM. Histological examination of rabbit ear veins showed that after local application with PYM lipsomal thermogels for 21 days, obvious vein thrombosis and inflammatory reaction could be observed. The above results indicated that PYM-loaded lipsomal CS/GP thermogels might have a good prospect for the treatment of VM.

Background: There is growing discussion of the relationship between health¬–related quality of life (HRQoL) and patient survival, which has been going on for the last few decades. Clinicians´ greatest wish is to extend the latter while improving the former. After neck dissection of early–stage oral carcinoma, “shoulder syndrome” appears due to traction of the accessory nerve during removal of level Ⅱb, which greatly affects patient quality of life. Since occult metastasis in level Ⅱb of early–stage oral carcinoma is extremely low, some surgeons suggest that level Ⅱb can be exempt from dissection to improve HRQoL. However, other surgeons take the opposite view, and thus there is no consensus on the necessity of Ⅱb dissection in T1–2N0M0 oral squamous¬ cell carcinoma (OSCC). Methods: We designed a parallel–group, randomized, non–inferiority trial that is supported by Shanghai Ninth People´s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China. We will enroll 522 patients of early oral carcinoma who match the inclusion criteria, and compare differences in 3–year overall survival, progression–free survival (PFS) and in HRQoL under different interventions (retention or dissection of level Ⅱb) between two groups. The primary end points will be tested by means of two-sided log-rank tests. Analysis of overall and progression–free survival will be performed in subgroups that were defined according to stratification factors with the use of univariate Cox analysis. In addition, we will use post hoc subgroup analyses on the basis of histological factors that were known to have effects on survival, such as death of invasion of the primary tumor. To evaluate HRQoL, we will choose the Constant–Murley scale to measure shoulder function. Discussion: Currently, there are no RCTs with large sample sizes on the necessity of IIb dissection in T1–T2N0M0 OSCC. We designed this reasonable non–inferiority RCT that combines survival rate and HRQoL to assess the feasibility of IIb neck dissection. The result of this trial may guide clinical practice and change the criteria of how early–stage oral cancer is managed. The balance between survival and HRQoL in this trial is based on early-stage breast cancer treatment and may provide new ideas for other malignancies.

A number of studies have reported the upregulation and functional roles of Jumonji domain-containing protein 6 (JMJD6) in various types of cancer. However, little is known regarding the clinical significance of JMJD6 in head and neck squamous cell carcinoma (HNSCC), particularly in terms of large-cohort data. In the present study, bioinformatics analysis was performed, using the University of California Santa Cruz Xena Browser and the Gene Expression Profiling Interactive Analysis 2 server, based on the Cancer Genome Atlas HNSCC cohort. In addition, a validation cohort was constructed based on 98 HNSCC cases. JMJD6 overexpression and knockdown, colony-formation, Transwell and cell viability assays were performed. JMJD6 was highly expressed in HNSCC samples and was associated with advanced pathological stage. However, no significant association was observed between JMJD6 expression levels and overall survival or disease-free survival times of patients with HNSCC. Subsequent in vitro assays indicated that overexpression of JMJD6 promoted malignant progression of HNSCC, by regulating epithelial-mesenchymal transition. Nevertheless, JMJD6 overexpression had no significant effects on the viability of HNSCC cells treated with 5-fluorouracil or cisplatin. Thus, it can be concluded that JMJD6 may function as a marker of HNSCC at advanced stage, however with no effect on drug resistance or prognosis. For patients with advanced HNSCC and high JMJD6 expression, rational chemotherapy may be more beneficial than radical surgery, considering their quality of life.

Exposure to ambient fine particular matter (PM2.5) are linked to an increased risk of metabolic disorders, leading to enhanced rate of many diseases, such as inflammatory bowel disease (IBD), cardiovascular diseases, and pulmonary diseases; nevertheless, the underlying mechanisms remain poorly understood. In this study, BALB/c mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CPM) for 2 months using a versatile aerosol concentration enrichment system(VACES). We found subchronic CPM exposure caused significant lung and intestinal damage, as well as systemic inflammatory reactions. In addition, serum and BALFs (bronchoalveolar lavage fluids) metabolites involved in many metabolic pathways in the CPM exposed mice were markedly disrupted upon PM2.5 exposure. Five metabolites (glutamate, glutamine, formate, pyruvate and lactate) with excellent discriminatory power (AUC = 1, p 0.001) were identified to predict PM2.5 exposure related toxicities. Furthermore, subchronic exposure to CPM not only significantly decreased the richness and composition of the gut microbiota, but also the lung microbiota. Strong associations were found between several gut and lung bacterial flora changes and systemic metabolic abnormalities. Our study showed exposure to ambient PM2.5 not only caused dysbiosis in the gut and lung, but also significant systemic and local metabolic alterations. Alterations in gut and lung microbiota were strongly correlated with metabolic abnormalities. Our study suggests potential roles of gut and lung microbiota in PM2.5 caused metabolic disorders.

Purpose Cystadenocarcinoma (CAC) is an extremely rare disease in parotid gland. This study aimed to identify the clinical characteristics of CAC, and the therapeutic options for its treatment. An attempt was also made to identify postoperative recurrence-related risk factors. Material and methods A retrospective study was conducted of CAC patients treated between 2008 and 2018. Predictive factors for postoperative recurrence (5-year RFS rate) were preliminarily filtered by Kaplan–Meier analysis and then further confirmed by a Cox regression model. Postoperative recurrence was defined as the primary outcome variable and was measured using both univariate and multivariate analysis. Results A total of 27 patients were analyzed, and the total incidence of postoperative recurrence was 33.3% (9/27). In the Cox regression analysis, patients who received a superficial parotidectomy were 0.046 times more likely to develop tumor relapse than those who only underwent enucleation (p = 0.032; 95% CI: 0.003–0.070). The chances of tumor recurrence in patients with the cribriform subtype were 9.701 times that for cases with a papillary pattern (p = 0.016; 95% CI: 1.517–62.030). The risk of postoperative recurrence increased abruptly, with an OR of 6.373 (p = 0.042; 95% CI: 1.070–37.965), when LN metastasis was found in patients. Conclusion Preoperative diagnosis of CAC in parotid gland is extremely important for allowing surgeons to apply appropriate therapeutic strategies (enucleation or superficial parotidectomy). Patients with LN metastasis, cribriform pattern, and Ki-67 positivity should be treated further to avoid tumor relapse.

Pingyangmycin (PYM) is an effective drug to treat vascular malformations (VM), but can easily diffuse from the injection site, which will reduce its therapeutic effect and increase side effect. Our study was to evaluate PYM-loaded chitosan thermogels for sustained and localized embolization therapy. It was shown that in vitro release of PYM thermogels could be delayed up to 12 days. The results measured by MTT assay showed that PYM thermogels could inhibit proliferation and induce apoptosis of EA.hy926 cells in a concentration and time dependent manner. In vivo pharmacokinetics study demonstrated that compared with PYM injections, PYM thermogels had a better sustained delivery of PYM. Macroscopic observation and histological examination of rabbit ear veins displayed that after administration with PYM thermogels for 18 days, obvious venous embolization and inflammatory response could be found. These results indicate that PYM thermogels is likely to achieve excellent prospects for VM treatment.

The Rigid Internal Fixation is one of the commonly used methods to reconstruct the mandible in bone repair surgery. This research proposed a complete flow of the designing and Finite Element Analysis (FEA).The customized titanium plate and screws model were imported in Mimics, then fitted and simulated with the shape of mandible 3D model. The simulation model would be imported into Magic's and the screw holes were located and punched. In order to ensure the validity of model for surgical guidance, the FEA was employed by FEA software Abaqus in this study. Different angles were selected and different loads were loaded. Comparing with the nomal mandible mechanical data, the von mises stress and deformation which was from the reconstruction of mandible were in the regular range and the RP model which would be used in the medical guidence was manufactured according to the 3D model. The research for this processing has important guide significance and good business prospects.

Mandibular defects need customized titanium plates for reconstruction. The conventional design process of titanium plate is prior to surgical interventions. The efficiency and accuracy of the conventional method is mainly dependent on experiences and skills of the designer. In order to decrease the dependence on design experience and enhance the participation of surgeons in the design process, designing and fabricating a customized titanium plate implant according to Rapid Prototyping (RP) biomedical model could be employed. RP biomedical model is greatly convenient to diagnosis and treatment planning. It could decrease the operation time and the risk of misinterpretation of the medical problem. In these cases, the operation time was reduced by 1.5–2.5 hours. A physical biomedical model also facilitates surgery planning and makes the rehearsal and simulation of the operation possibly. The customized titanium plate shape conforms to the patient's mandible anatomy and is thick enough to provide the strength and stiffness needed to fix the mandible until the bone grafts and soft tissues heal. At the same time it is thin enough to avoid extensive intrusion into soft tissues and to avoid weighing too much for the patient's jaw.