An Essential Role of Maspin in Embryogenesis and Tumor Suppression—Response

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An Essential Role of Maspin in Embryogenesis and Tumor Suppression—Letter

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Basal-A Triple Negative Breast Cancer Cells Selectively Rely on RNA Splicing for Survival

Prognosis of triple-negative breast cancer (TNBC) remains poor. To identify shared and selective vulnerabilities of basal-like TNBC, the most common TNBC subtype, a directed siRNA lethality screen was performed in 7 human breast cancer cell lines, focusing on 154 previously identified dependency genes of one TNBC line. Thirty common dependency genes were identified, including multiple proteasome and RNA splicing genes, especially those associated with the U4/U6.U5 tri-snRNP complex (e.g., PRPF8, PRPF38A). PRPF8 or PRPF38A knockdown or the splicing modulator E7107 led to widespread intronic retention and altered splicing of transcripts involved in multiple basal-like TNBC dependencies, including protein homeostasis, mitosis and apoptosis. E7107 treatment suppressed the growth of basal-A TNBC cell line and patient-derived basal-like TNBC xenografts at a well-tolerated dose. The anti-tumor response was enhanced by adding the proteasome inhibitor bortezomib. Thus, inhibiting both splicing and the proteasome might be an effective approach for treating basal-like TNBC.

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Death by HDAC inhibition in synovial sarcoma cells

Conventional cytotoxic therapies for synovial sarcoma provide limited benefit, and no drugs specifically targeting the causative SS18-SSX fusion oncoprotein are currently available. Histone deacetylase (HDAC) inhibition has been shown in previous studies to disrupt the synovial sarcoma oncoprotein complex, resulting in apoptosis. To understand the molecular effects of HDAC inhibition, RNA-Seq transcriptome analysis was undertaken in six human synovial sarcoma cell lines. HDAC inhibition induced pathways of cell cycle arrest, neuronal differentiation and response to oxygen-containing species, effects also observed in other cancers treated with this class of drugs. More specific to synovial sarcoma, polycomb-group targets were reactivated including tumor suppressor CDKN2A, and pro-apoptotic transcriptional patterns were induced. Functional analyses revealed that ROS-mediated FOXO activation and pro-apoptotic factors BIK, BIM and BMF were important to apoptosis induction following HDAC-inhibition in synovial sarcoma. HDAC-inhibitor pathway activation results in apoptosis and decreased tumor burden following a 7-day quisinostat treatment in the Ptenfl/fl;hSS2 mouse model of synovial sarcoma. This study provides mechanistic support for a particular susceptibility of synovial sarcoma to HDAC inhibition as a means of clinical treatment.

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Interleukin 4 receptor-targeted pro-apoptotic peptide blocks tumor growth and metastasis by enhancing anti-tumor immunity

Cellular crosstalk between tumors and M2-polarized tumor-associated macrophages (TAMs) favors tumor progression. Upregulation of interleukin 4 receptor (IL4R) is observed in diverse tumors and TAMs. We tested whether an IL4R-targeted pro-apoptotic peptide could inhibit tumor progression. The IL4R-binding peptide (IL4RPep-1) preferentially bound to IL4R-expressing tumor cells and M2-polarized macrophages both in vitro and in 4T1 breast tumors in vivo. To selectively kill IL4R-expressing cells, we designed an IL4R-targeted pro-apoptotic peptide, IL4RPep-1-K, by adding the pro-apoptotic peptide (KLAKLAK)2 to the end of IL4RPep-1. IL4RPep-1-K exerted selective cytotoxicity against diverse IL4R-expressing tumor cells and M2-polarized macrophages. Systemic administration of IL4RPep-1-K inhibited tumor growth and metastasis in 4T1 breast tumor-bearing mice. Interestingly, IL4RPep-1-K treatment increased the number of activated cytotoxic CD8+ T cells while reducing the numbers of immunosuppressive regulatory T cells and M2-polarized TAMs. No significant systemic side effects were observed. These results suggest that IL4R-targeted pro-apoptotic peptide has potential for treating diverse IL4R-expressing cancers.

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The p97 inhibitor CB-5083 is a unique disrupter of protein homeostasis in models of Multiple Myeloma.

Inhibition of the AAA ATPase, p97, was recently shown to be a novel method for targeting the ubiquitin proteasome system (UPS) and CB-5083, a first in class inhibitor of p97, has demonstrated broad antitumor activity in a range of both hematological and solid tumor models. Here, we show that CB-5083 has robust activity against multiple myeloma (MM) cell lines and a number of in vivo MM models. Treatment with CB-5083 is associated with accumulation of ubiquitinated proteins, induction of the unfolded protein response (UPR) and apoptosis. CB-5083 decreases viability in MM cell lines and patient derived MM cells, including those with background proteasome inhibitor (PI) resistance.  CB-5083 has a unique mechanism of action that combines well with PIs which is likely owing to the p97-dependent retro-translocation of the transcription factor, Nrf1, which transcribes proteasome subunit genes following exposure to a PI. In vivo studies using clinically relevant MM models demonstrate that single-agent CB-5083 inhibits tumor growth and combines well with MM standard of care agents. Our preclinical data demonstrate the efficacy of CB-5083 in several MM disease models and provide the rationale for clinical evaluation as monotherapy and in combination in MM.

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Sudden sensorineural hearing loss in children and adolescents: Clinical characteristics and age-related prognosis

Publication date: Available online 6 September 2017
Source:Auris Nasus Larynx
Author(s): Jin Youp Kim, Jae Joon Han, Woong Sang Sunwoo, Ja-Won Koo, Seung-Ha Oh, Min-Hyun Park, Young Ho Kim
ObjectiveAlthough many studies have investigated sudden sensorineural hearing loss (SSNHL) in adults, there were few studies on SSNHL in the pediatric population; especially research on treatment and prognosis of pediatric SSNHL was limited. The aim of this study was to evaluate clinical characteristics, treatment outcomes and prognostic factors in children and adolescents with SSNHL.MethodsA retrospective review of medical records of 67 pediatric patients (67 ears) who had diagnosed with SSNHL at our hospitals was performed to analyze patients' clinical manifestations and audiograms. All patients were treated with high-dose systemic prednisolone (1mg/kg), and 17 of them underwent intratympanic steroid injection therapy. Audiological evaluation was carried out before and after treatment, and hearing recovery was defined as complete recovery and partial recovery according to Siegel's criteria. Patients were divided into two groups: childhood group (ages between 4 and 12 years old) and adolescence group (age>12years), and clinical characteristics and treatment outcomes were investigated. In addition, patients were divided into two groups according to degree of hearing recovery, and evaluation was made regarding possible prognostic factors.ResultsThe recovery rate in total 67 patients was 55.2%. The recovery rate of the childhood group was significantly lower than that of the adolescence group (p=0.038). While the presence of vertigo did not significantly correlate with prognosis (p=0.219), the presence of tinnitus was significantly associated with hearing recovery (p=0.005). Audiological assessment revealed that a low initial hearing threshold, high speech discrimination score, and descending type of audiogram were positively associated with hearing recovery (p=0.002, p=0.003, and p=0.029, respectively).ConclusionThe childhood group had worse treatment outcomes than the adolescence group. High initial hearing threshold and absence of tinnitus were poor prognostic factors of hearing recovery. Active treatment is required for patients with these poor prognostic factors and childhood patients with SSNHL.



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One-day low-intensity combined arm-leg (Cruiser) ergometer exercise intervention: cardiorespiratory strain and gross mechanical efficiency in one-legged and two-legged exercise.

This study aims to research whether there is a difference in cardiorespiratory variables and gross mechanical efficiency (GE) in healthy individuals during low-intensity one-legged and two-legged exercise on the combined arm-leg (Cruiser) ergometer and whether motor learning occurs. The outcome of this study will support the use of the Cruiser ergometer in future as a testing and training instrument in the rehabilitation of patients with a lower limb amputation. Twenty-eight healthy men participated in this randomized-controlled trial. One group (n=14) used one leg and both arms during the exercise and the other group (n=14) used both legs and both arms. All participants performed a 1-day low-intensity exercise protocol. This included a standardized pretest and post-test of three bouts of 4 min exercise at 40 W and an exercise intervention of seven bouts of 2x4 min exercise at 40 W. The one-legged and two-legged group differed significantly in the heart rate and GE between the pretest and post-test. At the post-test, the one-legged group showed motor learning. GE improved significantly in both groups over the duration of the three exercise bouts of the pretest, but it did not improve during the post-test. There are differences in cardiorespiratory variables and GE between one-legged and two-legged exercise on the Cruiser ergometer. When using this ergometer in the rehabilitation of patients with a lower limb amputation, it is important to consider these differences and the occurrence of motor learning. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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The Study of Calcium, Phosphonium, Magnesium, and Ferrum Concentration in Serum of Patients With Primary Trigeminal Neuralgia: Erratum

No abstract available

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Research and Clinical Application of Three-Dimensional Location of Amygdaloid Body

Abstract: Accurately representing the spatial location of the amygdaloid body can lay an anatomical basis for the neurosurgery operation for amputation of the amygdaloid body through lateral fissure approach. As we know, there are a number of nerve nucleuses and essential structures locating around amygdaloid body in our brain, especially optic tract. However, only few research had been done to protect these tissues or nerve nucleuses. Thus, we reconstructed the three-dimensional images of the amygdaloid body of the human brain and established a coordinate system. The morphological parameters of the amygdaloid body and the three-dimensional coordinate data were measured. The spherical coordinates (R, θ, ϕ) were constructed by calculating the azimuth angle, elevation angle, and the distance from the coordinates origin to each amygdaloid body centroid. Sixty people brain MRI images without any visible organic disease were used in our research to investigate the average level of related parameters. The authors selected a proper coordinate origin and measured the value of anteroposterior diameter, right-and-left diameter, vertical diameter of the amygdaloid body, and the distance from the optic tract to amygdaloid body. The authors also measured the three-dimensional coordinate data of each centroid of the amygdaloid body in order to provide anatomical suggestion for surgery. The authors confirmed the nearest point from the foremost edge of the brain ventricle temporal horn to the lateral fissure, then viewed it as the coordinate origin. By means of coordinate translation, the authors got various morphological parameters and the coordinate values of each centroid of the amygdaloid body. Spherical coordinates were calculated from the three-dimensional coordinate values. The distances between the different layers of the amygdaloid body and the optic tract were also measured. The reconstruction of the three-dimensional coordinates of amygdaloid body is part of the digital engineering of the human body. The measurement of the parameters provides an important theoretical basis for the clinical amygdaloid body destruction surgery. Finally, the authors get conclusions as follows. There are no significant differences in the measured values of r1, r2, and r3 between the upper and lower diameters, the left and right diameters, the anteroposterior diameter of the amygdaloid body. The measured values of men and women are not statistically significant (P > 0.05). Spherical coordinates (R, θ, ϕ) calculated from the three-dimensional coordinate values and values from different sexes of the amygdaloid body are not statistically significant, either (P > 0.05). The distance between the different levels of the amygdaloid body and the optic tract (h1, h2, h3, h4, h5, h6, and h7) are not statistically significant (P > 0.05).

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The Current Challenge for Plastic and Reconstructive Surgery in China, the Biggest Developing Country

No abstract available

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Intracranial Enterogenous Cysts Close to the Brainstem Treated Through the Nerve Endoscope

Abstract: Enterogenous cysts (ECs) are rare, inborn lesions of central nervous system, which mostly occurred in the ventral side of the spinal cord as well as common in children; adult intracranial cysts are rare. Although the morbidity of intracranial ECs is quite low, we also can make a preliminary diagnosis of those patients with the help of imaging examination. In this article, we introduced 1 case of ECs ventral to the brainstem, which present images on magnetic resonance imaging as hypointense lesions on T1-weighted and high-intensity mass on T2-weighted image. In consideration of the difficulty of the surgical approach and the surgical visual field exposure, we use microscope and nerve endoscope to design personalized surgical approach to minimize the surgical injury. Pathologic examination showed that it was typical EC. Not only is the location extremely rare, but also the surgical method is uncommon in this disease. We not only study the intracranial ECs' manifestations, but also discuss the surgical approach and the application of nerve endoscope of our choice,which aims to provides a new surgical therapeutic approach for these lesions.

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Global Medical Cooperation With the East and West: Achieve Excellence in Craniofacial Surgery

No abstract available

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Three-Dimensional Radiologic Study on Index Measurement of Endonasal Endoscopic Optic Nerve Decompression

Objective: To provide the radiologic basis for the clinical application of endonasal endoscopic optic nerve decompression (EEOND). Methods: CTA images were used to observe the optic canal (OC) and related structures of 60 patients (120 sides) with normal nasal, paranasal sinuses, OC, and other related structures. Results: Optic canal could be classified as: the canal (10 sides, 8.33%), the semicanal (25 sides, 20.83%), the impression (49 sides, 40.83%), and the nonimpression (36 sides, 30%). According to its relationships with the sinuses, OC could be further typed as: ethmoid sinus (22 sides, 18.3%), sphenoid sinus (38 sides, 31.7%), ethmoid and sphenoid sinus (60 sides, 50%). The thickness of OC medial wall is about 1.11 ± 0.24 mm at orbital mouth, 0.87 ± 0.25 mm at middle part and 1.19 ± 0.27 mm at cranial mouth. The arc length of OC bone wall which can be opened from the sinus cavity is about 7.18 ± 0.76 mm at orbital mouth, 8.27 ± 0.93 mm at middle part, and 6.98 ± 0.89 mm at cranial mouth. The length of the OC medial wall is 12.18 ± 1.35 mm. In the three-dimensional Cartesian coordinate system that origined with the last point of middle turbinate root and oriented by temporal side, front side, and superior side, the coordinates of midpoints of OC medial wall are: (3.64 ± 1.11, 8.48 ± 1.65, 23.14 ± 2.67) at orbital mouth, (0.16 ± 1.21, 3.99 ± 1.80, 24.85 ± 2.67) at middle part, and (−3.59 ± 1.22, 0.77 ± 2.13, 26.39 ± 2.68) at cranial mouth. One length unit on the axes is a millimeter. Conclusion: Computed tomography (CT) scanning technique can measure the data of the OC in EEOND. It has great guiding significance for clinical operation.

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The Excellence of Graduate Medical Education in China: the New Door to Open for the Future of Young Surgeons

No abstract available

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Eyelid and Periorbital Surgery, Second Edition, edited by Mark A. Codner and Clinton D. McCord, Jr Boca Raton, FL: CRC Press, 2016

No abstract available

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Global Craniofacial Care

No abstract available

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Comprehensive Treatment of Primary Orbital Arteriovenous Malformation

Abstract: Primary orbital arteriovenous malformations are a rare kind of vascular malformation lesions. The authors present a 17-year-old man presented with swelling and pulsation in the left upper eyelid. The angiogram of the left internal carotid artery showed that arteriovenous malformations at the left upper eyelid area were supplied with one of the branches of ophthalmic artery. In this report, the authors elaborated the comprehensive treatments of primary arteriovenous malformation.

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Meet Dr Kilner at the Hunterian Museum

No abstract available

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Relative Location of Fundus Meatus Acustici Interni Via Porus Acusticus Internus in Facial Nerve Decompression

Abstract: Facial neural edema is the pathophysiological base of Bell's palsy. The middle cranial fossa approach is used to relieve the oppression of facial nerve at its most narrow course in the facial canal. In this research, the authors mainly discussed the internal auditory canal segment of facial nerve, completely in the shadow of the bony structure, which is inconvenient for transmastoid decompression. Therefore, the objective was to explore the definite position of the fundus meatus acustici interni from internal acoustic pore. Two hundred persons (age 22–60, 100 men and 100 women), presenting with healthy facial nerve, ear, and internal auditory canal, were investigated by computed tomography 3-dimensional reconstruction. Using statistical method to analyze, the authors obtained the definite position of the fundus meatus acustici interni, regarding the internal acoustic pore as the origin of coordinates. Our data provided more significant information for medical workers to improve the efficiency of operation and to prevent complications of surgery.

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