1.Emerging roles of Aurora-A kinase in cancer therapy resistance.
Dayong ZHENG ; Jun LI ; Han YAN ; Gang ZHANG ; Wei LI ; Edward CHU ; Ning WEI
Acta Pharmaceutica Sinica B 2023;13(7):2826-2843
Aurora kinase A (Aurora-A), a serine/threonine kinase, plays a pivotal role in various cellular processes, including mitotic entry, centrosome maturation and spindle formation. Overexpression or gene-amplification/mutation of Aurora-A kinase occurs in different types of cancer, including lung cancer, colorectal cancer, and breast cancer. Alteration of Aurora-A impacts multiple cancer hallmarks, especially, immortalization, energy metabolism, immune escape and cell death resistance which are involved in cancer progression and resistance. This review highlights the most recent advances in the oncogenic roles and related multiple cancer hallmarks of Aurora-A kinase-driving cancer therapy resistance, including chemoresistance (taxanes, cisplatin, cyclophosphamide), targeted therapy resistance (osimertinib, imatinib, sorafenib, etc.), endocrine therapy resistance (tamoxifen, fulvestrant) and radioresistance. Specifically, the mechanisms of Aurora-A kinase promote acquired resistance through modulating DNA damage repair, feedback activation bypass pathways, resistance to apoptosis, necroptosis and autophagy, metastasis, and stemness. Noticeably, our review also summarizes the promising synthetic lethality strategy for Aurora-A inhibitors in RB1, ARID1A and MYC gene mutation tumors, and potential synergistic strategy for mTOR, PAK1, MDM2, MEK inhibitors or PD-L1 antibodies combined with targeting Aurora-A kinase. In addition, we discuss the design and development of the novel class of Aurora-A inhibitors in precision medicine for cancer treatment.
2.The Effects of Hyperbaric Oxygen Therapy in Patients with Central Retinal Artery Occlusion: A Retrospective Study, Systematic Review, and Meta-analysis
Luca ROSIGNOLI ; Edward R. CHU ; John E. CARTER ; Daniel A. JOHNSON ; Jeong-Hyeon SOHN ; Sepehr BAHADORANI
Korean Journal of Ophthalmology 2022;36(2):108-113
Purpose:
Central retinal artery occlusion (CRAO) is a vision-threatening condition with a potentially poor visual prognosis. Many different treatment modalities are suggested but controversy remains regarding effectiveness of these treatments. The purpose of this study is to perform a systematic review and meta-analysis in addition to analyzing retrospective data at our own tertiary care center regarding effectiveness of hyperbaric oxygen therapy (HBOT) in treatment of CRAO.
Methods:
The PubMed, Scopus, and the Cochrane Library are searched from the date of database inception to September 2021 to conduct a review based on the PRISMA (preferred reporting items for systematic review and meta-analysis), evaluating the role of HBOT in visual recovery of CRAO patients. In addition, a retrospective chart review of patients clinically diagnosed with CRAO at our university-based hospital (University of Texas Health, San Antonio, TX, USA) from year 2011 to 2021 was conducted.
Results:
After a review of 376 articles, three articles met the inclusion criteria for meta-analysis, where a total of 207 patients received HBOT versus 89 patients that did not receive any form of oxygen therapy. Analysis of these results demonstrate that HBOT in CRAO patients does not enhance the final visual outcome (p = 0.83). Similar conclusion was also drawn from retrospective analysis of 48 patients (15 HBOT versus 33 controls) at our tertiary care center, where no visual benefit was observed in the HBOT group.
Conclusions
HBOT does not appear to improve final visual outcome and concerns remain regarding adverse reactions such as barotrauma and generalized seizures. Large, randomized studies are required for further understanding of the role of HBOT in treatment of CRAO.
3.Association between High Diffusion-Weighted Imaging-Derived Functional Tumor Burden of Peritoneal Carcinomatosis and Overall Survival in Patients with Advanced Ovarian Carcinoma
He AN ; Jose AU PERUCHO ; Keith WH CHIU ; Edward S HUI ; Mandy MY CHU ; Siew Fei NGU ; Hextan YS NGAN ; Elaine YP LEE
Korean Journal of Radiology 2022;23(5):539-547
Objective:
To investigate the association between functional tumor burden of peritoneal carcinomatosis (PC) derived from diffusion-weighted imaging (DWI) and overall survival in patients with advanced ovarian carcinoma (OC).
Materials and Methods:
This prospective study was approved by the local research ethics committee, and informed consent was obtained. Fifty patients (mean age ± standard deviation, 57 ± 12 years) with stage III–IV OC scheduled for primary or interval debulking surgery (IDS) were recruited between June 2016 and December 2021. DWI (b values: 0, 400, and 800 s/mm2 ) was acquired with a 16-channel phased-array torso coil. The functional PC burden on DWI was derived based on K-means clustering to discard fat, air, and normal tissue. A score similar to the surgical peritoneal cancer index was assigned to each abdominopelvic region, with additional scores assigned to the involvement of critical sites, denoted as the functional peritoneal cancer index (fPCI). The apparent diffusion coefficient (ADC) of the largest lesion was calculated. Patients were dichotomized by immediate surgical outcome into high- and low-risk groups (with and without residual disease, respectively) with subsequent survival analysis using the Kaplan-Meier curve and log-rank test. Multivariable Cox proportional hazards regression was used to evaluate the association between DWI-derived results and overall survival.
Results:
Fifteen (30.0%) patients underwent primary debulking surgery, and 35 (70.0%) patients received neoadjuvant chemotherapy followed by IDS. Complete tumor debulking was achieved in 32 patients. Patients with residual disease after debulking surgery had reduced overall survival (p = 0.043). The fPCI/ADC was negatively associated with overall survival when accounted for clinicopathological information with a hazard ratio of 1.254 for high fPCI/ADC (95% confidence interval, 1.007–1.560; p = 0.043).
Conclusion
A high DWI-derived functional tumor burden was associated with decreased overall survival in patients with advanced OC.
4.Prevalence and risk factors for human papillomavirus infection among female sex workers in Hanoi and Ho Chi Minh City, Viet Nam: a cross-sectional study
Quang Duy Pham ; Kiesha Prem ; Tuan Anh Le ; Nguyen Van Trang ; Mark Jit ; Tuan Anh Nguyen ; Van Cao ; Tam-Duong Le-Ha ; Mai Thi Ngoc Chu ; Ly Thi Khanh Le ; Zheng Quan Toh ; Marc Brisson ; Suzanne Garland ; Gerald Murray ; Kathryn Bright ; Duc Anh Dang ; Hau Phuc Trana ; Edward Kim Mulholland
Western Pacific Surveillance and Response 2022;13(4):1-11
Objective:
Female sex workers (FSWs) are at high risk of human papillomavirus (HPV) infections and cervical cancer due to their high number of sexual partners. The objectives of this study were to determine the prevalence of HPV and identify risk factors for high-risk HPV infection among FSWs in Hanoi and Ho Chi Minh City (HCMC), Viet Nam.
Methods:
A cross-sectional study was conducted in Hanoi and HCMC between December 2017 and May 2018. We surveyed and screened 699 FSWs aged ≥18 years for HPV infection and abnormal cytology. A multivariable modified Cox regression model was used to determine risk factors for high-risk HPV infection.
Results
The overall prevalence of any HPV, high-risk HPV and HPV-16/18 infection in the 699 FSWs was 26.3%, 17.6% and 4.0%, respectively, and were similar in both cities. Multiple infections were identified in 127 participants (69.0%).HPV-52 was the most prevalent (7%), followed by HPV-58 (6%). Abnormal cytology was detected in 91 participants (13.0%). FSWs who are divorced (adjusted prevalence ratio [aPR]: 1.96, 95% confidence interval [CI]: 1.01–3.81), widowed (aPR: 3.26, 95% CI: 1.49–7.12) or living alone (aPR: 1.85, 95% CI: 1.01–3.39) were associated with a higher prevalence of high-risk HPV infection.
5.Protective Role of 360° Laser Retinopexy in Patients with Rhegmatogenous Retinal Detachment: a Systematic Review and Meta-analysis
Christa SOEKAMTO ; Edward R CHU ; Daniel A JOHNSON ; Jeong-Hyeon SOHN ; Sepehr BAHADORANI
Korean Journal of Ophthalmology 2021;35(3):215-222
Purpose:
Visual impairment from retinal re-detachment could be debilitating. The aim of this review is to evaluate the role of 360° laser retinopexy on success rate of rhegmatogenous retinal detachment (RRD) repair by a meta-analysis study.
Methods:
The PubMed, Scopus, and the Cochrane Library databases were searched comprehensively from the date of database inception to January 2021, evaluating the role of 360° laser retinopexy in visual and anatomical success rate of RRD repair. This review was conducted based on the preferred reporting items for systematic review and meta-analysis (PRISMA) protocols.
Results:
Among 202 articles screened for eligibility, six studies were found to be eligible for inclusion in our final analysis. Our meta-analysis demonstrates that prophylactic treatment with circumferential laser photocoagulation has no significant effect on the initial rate of retinal re-detachment or final best-corrected visual acuity following pars plana vitrectomy repair of RRD. Subgroup analysis of studies (n = 3) with 23-gauge pars plana vitrectomy, however, favors attachment rate in patients undergoing 360° prophylactic laser treatment.
Conclusions
Three hundred and sixty degree laser retinopexy appears to have favorable outcomes in patients undergoing 23-gauge retinal detachment repair. This protective effect, however, is not apparent with inclusion of 20-gauge vitrectomy studies.
6.Protective Role of 360° Laser Retinopexy in Patients with Rhegmatogenous Retinal Detachment: a Systematic Review and Meta-analysis
Christa SOEKAMTO ; Edward R CHU ; Daniel A JOHNSON ; Jeong-Hyeon SOHN ; Sepehr BAHADORANI
Korean Journal of Ophthalmology 2021;35(3):215-222
Purpose:
Visual impairment from retinal re-detachment could be debilitating. The aim of this review is to evaluate the role of 360° laser retinopexy on success rate of rhegmatogenous retinal detachment (RRD) repair by a meta-analysis study.
Methods:
The PubMed, Scopus, and the Cochrane Library databases were searched comprehensively from the date of database inception to January 2021, evaluating the role of 360° laser retinopexy in visual and anatomical success rate of RRD repair. This review was conducted based on the preferred reporting items for systematic review and meta-analysis (PRISMA) protocols.
Results:
Among 202 articles screened for eligibility, six studies were found to be eligible for inclusion in our final analysis. Our meta-analysis demonstrates that prophylactic treatment with circumferential laser photocoagulation has no significant effect on the initial rate of retinal re-detachment or final best-corrected visual acuity following pars plana vitrectomy repair of RRD. Subgroup analysis of studies (n = 3) with 23-gauge pars plana vitrectomy, however, favors attachment rate in patients undergoing 360° prophylactic laser treatment.
Conclusions
Three hundred and sixty degree laser retinopexy appears to have favorable outcomes in patients undergoing 23-gauge retinal detachment repair. This protective effect, however, is not apparent with inclusion of 20-gauge vitrectomy studies.
7.Retrospective analysis of 79 patients with orbital floor fracture: outcomes and patient-reported satisfaction.
Olivier SENESE ; Edward BOUTREMANS ; Caroline GOSSIAUX ; Isabelle LOEB ; Didier DEQUANTER
Archives of Craniofacial Surgery 2018;19(2):108-113
BACKGROUND: The aim of our retrospective study is to evaluate the management of isolated orbital floor fractures considering the clinical, functional and aesthetic results according to the surgical approach and the type of materials used. METHODS: Retrospectively, clinical, radiological, surgical, and ophthalmological data from 79 patients were collected from January 2010 to December 2016. Furthermore, included patients were interrogated on functional and aesthetic satisfaction. RESULTS: The main causes of trauma were physical aggression followed by accidents. The median time between trauma and surgery was 4 days. The most common surgical approaches were the subciliary and the transconjunctival ones. Alloplastic materials were used in 75 patients. In two patients, we used a combination of two grafts. Patients experienced minor immediate complications. On follow-ups, none of our patients suffered from ocular movement restrictions. Patients treated by subciliary approach had higher risk of retractile scaring compared to other surgical approaches. In our study, patients agreed to complete a questionnaire assessing functional and aesthetic outcomes with a high satisfaction score. No association between the implant material used and the results has been assessed. CONCLUSION: This study describes the results of orbital floor reconstructions. Despite a variety of materials used and surgical approaches performed, we believe that the transconjunctival approach is the most suitable option with a high satisfaction score.
Aggression
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Follow-Up Studies
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Humans
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Orbit*
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Retrospective Studies*
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Transplants

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