[The influence and mechanisms of lysine-specific demethylase 1 (LSD1) on invasion and metastasis of colon cancer cells].

Objective: To investigate the effect and molecular mechanisms of LSD1 on proliferation and metastasis of colon cancer. Methods: The influence of down-regulated LSD1 expression on proliferation, invasion and apoptosis of colon cancer cells were detected by transwell invasion assay, cell proliferation assay and apoptosis assay, respectively. Results: Three independent siRNAs targeting LSD1 (siRNA-1554, siRNA-705, and siRNA-1973) were transfected to SW620 cells to detect gene-silencing efficiency, and the result showed that the knockdown effect of siRNA-705 were better than the other two siRNAs at both mRNA and protein levels. Using siRNA-705 and pargyline (2.5 mmol/L), we performed transwell invasion assay, cell proliferation assay and apoptosis assay in SW620 cell lines, and found the significant suppression of invasion and growth. Cell apoptosis were induced by siRNA and pargyline (P<0.05). Interestingly, up-regulation of E-cadherin and down-regulation of N-cadherin were observed after treated with siRNA-705 and pargyline for 72 hours. Conclusion: Inhibition of LSD1 could impair proliferation and invasiveness, and induce apoptosis of colon cancer cells in vitro. It leads to up-regulation of E-cadherin and down-regulation of N-cadherin. All of above may play important roles in invasion and metastasis of colon cancer.

Bursts of Terahertz Radiation from Large-Scale Plasmas Irradiated by Relativistic Picosecond Laser Pulses.

Powerful terahertz (THz) radiation is observed from large-scale underdense preplasmas in front of a solid target irradiated obliquely with picosecond relativistic intense laser pulses. The radiation covers an extremely broad spectrum with about 70% of its energy located in the high frequency regime over 10 THz. The pulse energy of the radiation is found to be above 100 µJ per steradian in the laser specular direction at an optimal preplasma scale length around 40-50 µm. Particle-in-cell simulations indicate that the radiation is mainly produced by linear mode conversion from electron plasma waves, which are excited successively via stimulated Raman scattering instability and self-modulated laser wakefields during the laser propagation in the preplasma. This radiation can be used not only as a powerful source for applications, but also as a unique diagnostic of parametric instabilities of laser propagation in plasmas.

Inferior alveolar nerve function recovers after decompression of large mandibular cystic lesions.

OBJECTIVE: The treatment of large mandibular cystic lesions (diameter > 35 mm) is controversial. Few studies determine the inferior alveolar nerve function after decompression which is one of the major options for treating such lesions. We aim to investigate the recovery of inferior alveolar nerve function after decompression. METHODS: Twenty-two patients with large mandibular cystic lesions, diagnosed as keratocystic odontogenic tumor, ameloblastoma, or dentigerous cyst, were included. Inferior alveolar nerve function was observed by monitoring the pulp vitality of involved teeth (n = 64) with electric pulp test before decompression and 1, 3, 6, 9, 12, and 24 months after decompression, respectively. RESULTS: The pulp vitality of the involved teeth was significantly decreased before decompression. Recovery of pulp vitality could be observed after decompression, indicating the recovery of inferior alveolar nerve function. A majority (96.9%) of the vital pulp was preserved in the involved teeth after decompression. CONCLUSIONS: Recovery of inferior alveolar nerve function was remarkable in patients with large mandibular cystic lesions after decompression, indicated by the recovery of pulp vitality of involved teeth. When decompression is preferred, conservative therapy rather than root canal therapy is recommended for the teeth with root tip exposed in the cystic lesions and without pulposis.

Obatoclax induces Beclin 1- and ATG5-dependent apoptosis and autophagy in adenoid cystic carcinoma cells.

OBJECTIVES: Adenoid cystic carcinoma (ACC) is one of the most common salivary gland cancers. The prognosis of adenoid cystic carcinoma is poor for its high frequency of distant metastases and insensitivity to chemotherapy or molecular therapies. This study investigated the effect of Obatoclax on adenoid cystic carcinoma cells and its cytotoxic mechanism. METHODS: Western blot, transmission electron microscopy, and pEGFP-LC3 plasmids transfection were carried out to detect autophagy in ACC cells treated with Obatoclax. 3-MA and RNA interference against Beclin 1 and ATG5 were used to inhibit autophagy. Then we used Western blot and Hochest 33342 staining for apoptosis assessment. Finally, cell viability was assessed by MTT assay. RESULTS: We found that Obatoclax induced cytoprotective autophagy which depended on ATG5 and partly on Beclin 1 in adenoid cystic carcinoma cells. Furthermore, pharmacologically inhibiting Obatoclax-induced autophagy promoted apoptosis. Downregulation of Beclin 1 or ATG5 attenuated the cytotoxicity of Obatoclax by suppressing both autophagy and apoptosis. Finally, when apoptosis was pharmacologically inhibited, autophagic cell death was initiated in adenoid cystic carcinoma cells treated with Obatoclax. CONCLUSION: In summary, Beclin 1 and ATG5 play important roles in regulating both Obatoclax-induced autophagy and apoptosis in adenoid cystic carcinoma.

LSD1-mediated epigenetic modification contributes to proliferation and metastasis of colon cancer.

BACKGROUND: Emerging evidence has demonstrated that lysine-specific demethylase 1 (LSD1) has an important role in many pathological processes of cancer cells, such as carcinogenesis, proliferation and metastasis. In this study, we characterised the role and molecular mechanisms of LSD1 in proliferation and metastasis of colon cancer. METHODS: We evaluated the correlation of LSD1, CDH-1 and CDH-2 with invasiveness of colon cancer cells, and investigated the roles of LSD1 in proliferation, invasion and apoptosis of colon cancer cells. We further investigated the mechanisms of LSD1-mediated metastasis of colon cancer. RESULTS: Lysine-specific demethylase 1 was upregulated in colon cancer tissues, and the high LSD1 expression was significantly associated with tumour-node-metastasis (TNM) stages and distant metastasis. Functionally, inhibition of LSD1 impaired proliferation and invasiveness, and induced apoptosis of colon cancer cells in vitro. The LSD1 physically interacted with the promoter of CDH-1 and decreased dimethyl histone H3 lysine 4 (H3K4) at this region, downregulated CDH-1 expression, and consequently contributed to colon cancer metastasis. CONCLUSION: Lysine-specific demethylase 1 downregulates the expression of CDH-1 by epigenetic modification, and consequently promotes metastasis of colon cancer cells. The LSD1 antagonists might be a useful strategy to suppress metastasis of colon cancer.

Volumetric change of bony cavity and shrinkage speed after marsupialization for odontogenic keratocyst and unicystic ameloblastoma.

The aim of this study was to evaluate the efficacy of marsupialization treatment for odontogenic keratocyst (OKC) and unicystic ameloblastoma (UA) based on the three-dimensional volumetric change over time, and to determine the difference between OKC and UA in terms of the absolute volume reduction (AVR) and absolute shrinkage speed (ASS), and whether they are correlated with the preoperative volume, time after marsupialization (time between marsupialization and second treatment), and patient age. This was a retrospective cohort study with a sample size of 60 patients: 29 with OKC and 31 with UA. Pre- and post-marsupialization cone beam computed tomography images were analysed using Mimics software. The volume reduction and shrinkage speed were analysed and correlated with the preoperative volume, time after marsupialization, and demographic data. Descriptive univariable and multivariable statistics were computed; significance was set at P ≤ 0.05. The mean percentage volume reduction after marsupialization was 67.6 ± 9.6% for OKC and 63.3 ± 20.1% for UA. There was no significant difference in AVR or ASS between the OKC and UA groups. For OKC and UA, the preoperative volume (both P < 0.001) and time after marsupialization (P = 0.024 and P < 0.001, respectively) were associated with AVR. Moreover, for OKC and UA, the preoperative volume and time after marsupialization were also significantly associated with the ASS (all P < 0.001). For both lesions, patient age was not significantly related to AVR or ASS. Marsupialization appears to be a viable option to decrease the volume of OKC and UA. Age was found not to be associated with the volume reduction of either UA or OKC.

Myeloid-derived suppressor cells contribute to oral cancer progression in 4NQO-treated mice.

OBJECTIVE: Abnormal myelopoiesis especially the expansion of myeloid-derived suppressor cells (MDSCs) is increasingly recognized as an important reason for the escape of tumor from immune surveillance. This study aims to investigate the role of this specific population of cells in oral cancer progression. MATERIALS AND METHODS: 4-Nitroquinoline 1-oxide (4NQO) was used to induce oral cancer in C57BL/6 mice. The tongue mucosa was examined by hematoxylin and eosin staining. The distribution of MDSCs in the spleen and peripheral blood and T cell subsets in the spleen was analyzed by flow cytometry. The expression of MDSCs in the tongue tissues was investigated by immunohistochemical staining, and the expression of arginase-1 (ARG-1) and NOS-2 in the tongue tissues was detected by real-time PCR. RESULTS: We found that during tumor progression, significantly increased frequency of MDSCs was observed in the spleens and peripheral blood of 4NQO-treated mice, and the frequency of MDSCs in the spleens was positively correlated with systemic CD3(+) CD8(+) T cells. Moreover, 4NQO-treated mice showed significantly higher MDSCs infiltration and ARG-1 mRNA level in the tumor site. CONCLUSIONS: Myeloid-derived suppressor cells contribute to oral tumor progression and represent a potential target for immunotherapy of oral cancer.

Assessment of the contralateral facial artery pedicle nasolabial island flap for buccal defect repair.

The facial artery pedicle nasolabial island flap (FAPNIF) is widely used for oral and maxillofacial reconstruction. However, its use in reconstruction after malignant tumour resection is limited by the possibility of ipsilateral cervical lymph node metastasis along the facial artery. Through fine dissection, it was found that the contralateral FAPNIF can be used to repair the defect after buccal carcinoma resection. The aim of this study was to evaluate the clinical outcomes of the contralateral FAPNIF for buccal defect repair. From 2013 to 2016, 30 patients underwent the repair of a buccal defect with a contralateral FAPNIF after tumour resection. Clinical outcomes and complications were recorded and quality of life was evaluated preoperatively and at 3, 6, and 12 months postoperative. The flaps survived in all 30 cases. Mean mouth opening was 2.50±0.14cm at 1 month, 3.22±0.25cm at 6 months, and 3.35±0.23cm at 12 months postoperative. With regard to patient quality of life, adverse effects included impaired aesthetics, pain, and difficulty eating; these usually subsided within 1year after surgery. The contralateral FAPNIF is easily harvested and is a safe and effective option for the repair of medium-sized buccal defects after the resection of carcinoma.

Diagnostic value of intraoperative bone marrow assessment for bone margins in patients with head and neck squamous cell carcinoma: a systematic review and meta-analysis.

A clear bone margin is essential for complete resection of the bone-involved tumour, but the evaluation of hard tissue takes time and is impractical intraoperatively. Bone marrow assessment remains controversial. The aim of this study was to investigate the diagnostic value of intraoperative bone marrow assessment for bone margins. PubMed and Web of Science were searched for studies published between 1990 and 2017. A systematic review was conducted. After quality assessment, 10 articles with 11 cohorts and 404 patients were identified. Sensitivity, specificity, and other measures were pooled for meta-analysis; the estimates for intraoperative bone marrow assessment were as follows: sensitivity 0.82 (95% confidence interval (CI) 0.62-0.93), specificity 0.99 (95% CI 0.96-1.00), positive likelihood ratio 109.79 (95% CI 22.99-524.34), negative likelihood ratio 0.18 (95% CI 0.08-0.42), and diagnostic odds ratio 241.82 (95% CI 90.33-647.38). Furthermore, sensitivity and specificity at the summary operating point of the summary receiver operating characteristic curve were 0.82 and 0.99, respectively, and the area under the curve was 0.99. Intraoperative bone marrow assessment was investigated by meta-analysis and shown to have a high level of overall accuracy for the diagnosis of bone margins.

Genomic Signature of Mismatch Repair Deficiency in Areca Nut-Related Oral Cancer.

Areca nut (AN) chewing contributes to an increase of oral squamous cell carcinoma (OSCC) cases in South and Southeast Asia; however, genomic events underlying the carcinogenesis process of AN-related OSCC remain unclear. Here, we comprehensively describe the genomic and transcriptome alterations of 113 Chinese OSCC patients (89 AN related and 24 AN negative) by whole-exome sequencing and RNA sequencing, and we compared the genomic differences between AN-related and AN-negative samples by integrating sequencing data of 325 OSCC patients from The Cancer Genome Atlas database and 50 from a published Taiwanese study. We identified 11 significantly mutated genes for OSCC, including 4 novel ones (ATG2A, WEE1, DST, and TSC2), of which WEE1 and ATG2A mutated with significantly higher rates in AN-related samples (P = 0.04 and P = 0.003, respectively). Mutational signature analysis revealed that AN-related OSCCs were specially characterized by the genomic signature of mismatch repair deficiency (dMMR), which could also predict the prognosis status of AN-related OSCC. In addition, an elevated PD-L1 expression was also observed in both AN-related patients (P = 3.71 × 10-11) and those with a high dMMR level (P = 1.99 × 10-4). Further differential expression analysis and in vitro experiments confirmed the role of dMMR in the development of OSCC induced by AN exposure. Taken together, this study first revealed the molecular profiles and highlighted the role of dMMR in AN-related OSCC among the Chinese population and identified that AN-related OSCC may represent a potential cohort for effective anti-PD-1/L1 immunotherapy.

Risk factors and prognosis for the primary intraosseous carcinoma of the jaw.

Primary intraosseous carcinoma (PIOC) is a rare but aggressive type of odontogenic tumour arising within the jawbone. Diagnosis criteria and treatment strategy remain difficult and controversial. The present study aimed to clarify the clinicopathological features and determine prognostic factors in management of PIOC. A retrospective study of 30 patients with PIOC, treated at the Hospital of Stomatology of Sun Yat-sen University between 2009 and 2017, was conducted. Clinical, histopathological and treatment modality data were collected. Follow-up data were recorded to determine prognostic factors. There were 19 males and 11 females with a mean age of 52.3 years. The most common location of the tumour was the mandible (90%). Having a history of tooth extraction or tooth mobility was the major characteristic symptom (63.3%), jaw swelling coming in second (53.3%). Half of the patients underwent surgery alone. The estimated 2-year overall survival rate (OS) and recurrence-free survival rate (RFS) were 61.3% and 40.1%, respectively. Higher histological grade was an independent risk factor for poor OS (hazard ratio (HR) 0.233 [0.059-0.915], P=0.037), while at pN+ stage for RFS, HR=5.627 [1.199-26.409], P=0.029. Because of its rarity and intrabony site, the classification, staging and treatment guidelines for PIOC should be further studied and established.

Use of medial upper arm free flap in oral cavity reconstruction: a preliminary study.

The medial upper arm has previously been proposed as a potential free flap donor site, but the clinical application of such flaps in head and neck reconstruction has not been popular. The preliminary results of the clinical application of medial upper arm free flaps in oral cavity reconstruction are reported here. Five patients with oral cancer underwent surgical resection and neck dissection, with simultaneous reconstruction using a medial upper arm free flap. Functional outcomes were investigated using the University of Washington Quality of Life Questionnaire. Sensory-motor functions of the upper arm donor site were recorded before and after surgery. Four flaps were successfully transferred. One flap was abandoned during surgery because of a lack of perforators, and a forearm flap was used instead. All patients survived without loco-regional recurrence or distant metastasis. Functional outcomes, especially swallowing and speech, were satisfactory. The donor site scar was well hidden, with no functional impairment. This initial experience shows that the medial upper arm free flap represents an alternative perforator flap for oral cavity microsurgical reconstruction. The well-hidden scar and better texture match compared with other flaps make it suitable for oral cavity reconstruction.

Cherenkov radiation-based optical fibre diagnostics of fast electrons generated in intense laser-plasma interactions.

Diagnosing fast electrons is important to understand the physics underpinning intense laser-produced plasmas. Here, we demonstrate experimentally that a Cherenkov radiation-based optical fibre can serve as a reliable diagnostic to characterize the fast electrons escaping from solid targets irradiated by ultra-intense laser pulses. Using optical fibre loops, the number and angular distributions of the escaping electrons are obtained. The data agree well with measurements made using image plate stacks. The optical fibre can be operated at high-repetition rates and is insensitive to x-rays and ion beams, which makes it advantageous over other routinely used fast electron diagnostics in some aspects.

Neutron yield enhancement in laser-induced deuterium-deuterium fusion using a novel shaped target.

Neutron yields have direct correlation with the energy of incident deuterons in experiments of laser deuterated target interaction [Roth et al., Phys. Rev. Lett. 110, 044802 (2013) and Higginson et al., Phys. Plasmas 18, 100703 (2011)], while deuterated plasma density is also an important parameter. Experiments at the Shenguang II laser facility have produced neutrons with energy of 2.45 MeV using d (d, n) He reaction. Deuterated foil target and K-shaped target were employed to study the influence of plasma density on neutron yields. Neutron yield generated by K-shaped target (nearly 10(6)) was two times higher than by foil target because the K-shaped target results in higher density plasma. Interferometry and multi hydro-dynamics simulation confirmed the importance of plasma density for enhancement of neutron yields.

Intraurethral brachytherapy for prevention of recurrent urethral stricture after internal urethrotomy or transurethral resection of scar.

BACKGROUND PURPOSE: Restricture after internal urethrotomy is the major limitation to the long-term success of the procedure. The objective of this study was to evaluate the effect of intraurethral brachytherapy after internal urethrotomy or transurethral scar resection on recurrent urethral stricture. PATIENTS AND METHODS: From January 1998 to June 1999, catheter-based intraurethral brachytherapy with 192-iridium was performed in 17 patients with recurrent urethral stricture to prevent restricture after internal urethrotomy or transurethral resection of scar. The radiation was repeated within 3 days after surgery to reach a total dosage of 1000 to 1500 cGy. RESULTS: During the follow-up (range 14-27 months; mean 20 months), two patients had dysuria, including one patient with an atonic detrusor muscle. The other patient needed self-dilation. Fifteen patients presented normal voiding. The stricture recurred 3 months later in only one patient, so the restricture rate is 7%. No significant complication was observed associated with brachytherapy during the follow-up. CONCLUSION: Intraurethral brachytherapy after internal urethrotomy or transurethral resection of scar is a safe and effective treatment for recurrent urethral strictures.

Healing masseter entheses of mandibular reconstruction with autograft--Raman spectroscopic and histological study.

Autogenous bone graft represents the gold standard for mandibular reconstruction. The authors used a beagle mandibular defect model and reconstructed with iliac crest and ulna graft. Healing masseter entheses were harvested 24 weeks after surgery and analyzed by histology and Raman microspectroscopy. The intensity ratio of 960/2940 was to document mineral-to-collagen ratio as degree of mineralization. Pearson correlation was used to evaluate the association between the intensity ratios of 960/2940 and the tendon-to-bone insertion site. In the normal control group (n=4) and the experimental control group with detached masseter muscle (n=4), the degree of mineralization at the insertion site increased linearly from tendon to bone. In the iliac graft (n=4) and ulna graft groups (n=4), healing entheses were far less mature than controls and a linear trend was not observed. There was no significant correlation between degree of mineralization and insertion site in the ulna group (r(spearman)=0.519, P>0.001). These results indicate that transplanted bone plays a critical role in healing of entheses and healing enthesis to reconstructed mandible is inferior to normal. Raman spectroscopy provides quantitative information about different healing entheses and gives valuable insight into mechanical properties of entheses in functional mandibular reconstruction.

Spectrally peaked electron beams produced via surface guiding and acceleration in femtosecond laser-solid interactions.

Highly collimated MeV electron beam guiding has been observed along the target surface following the interaction of bulk target irradiation by femtosecond laser pulses at relativistic intensities. The beam quality is shown to depend critically on the laser contrast: With a ns prepulse, the generated electron beam is well concentrated and intense, while a high laser contrast produces divergent electron beams. In the case of large preplasma scale lengths, tunable guiding and acceleration of the target surface electrons is achieved by changing the laser incident angle. By expanding the preplasma scale length to several hundred micrometers, we obtained MeV spectrum-peaked electron beams with a 100 pC per laser pulse and divergence angles of only 3°. This technique suggests a stable method of injection of elections into a variety of accelerator designs.