Pan-cancer Analysis of Tumor Mutational Burden and Homologous Recombination DNA Damage Repair Using Targeted Next-Generation Sequencing

Hai-Yun Wang,Ling Deng,Ying-Qing Li,Xiao Zhang,Ya-Kang Long,Xu Zhang,Yan-Fen Feng,Yuan He,Tao Tang,Xin-Hua Yang,Fang Wang 대한암학회 2021 Cancer Research and Treatment Vol.53 No.4

Purpose Current variability in methods for tumor mutational burden (TMB) estimation and reporting demonstrates the urgent need for a homogeneous TMB assessment approach. Here, we compared TMB distributions in different cancer types using two customized targeted panels commonly used in clinical practice. Materials and Methods TMB spectra of 295- and 1021-gene panels in multiple cancer types were compared using targeted next-generation sequencing (NGS). The TMB distributions across a diverse cohort of 2,332 cancer cases were then investigated for their associations with clinical features. Treatment response data were collected for 222 patients who received immune-checkpoint inhibitors (ICIs) and their homologous recombination DNA damage repair (HR-DDR) and programmed death-ligand 1 (PD-L1) expression were additionally assessed and compared with the TMB and response rate. Results The median TMB between gene panels was similar despite a wide range in TMB values. The highest TMB was eight and 10 in patients with squamous cell carcinoma and esophageal carcinoma according to the classification of histopathology and cancer types, respectively. Twenty-three out of 103 patients (22.3%) were HR-DDR–positive and could benefit from ICI therapy; out of those 23 patients, seven patients had high TMB (p=0.004). Additionally, PD-L1 expression was not associated with TMB or treatment response among patients receiving ICIs. Conclusion Targeted NGS assays demonstrated the ability to evaluate TMB in pan-cancer samples as a tool to predict response to ICIs. In addition, TMB integrated with HR-DDR–positive status could be a significant biomarker for predicting ICI response in patients.

Prediction Models for Solitary Pulmonary Nodules Based on Curvelet Textural Features and Clinical Parameters

Wang, Jing-Jing,Wu, Hai-Feng,Sun, Tao,Li, Xia,Wang, Wei,Tao, Li-Xin,Huo, Da,Lv, Ping-Xin,He, Wen,Guo, Xiu-Hua Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.10

Lung cancer, one of the leading causes of cancer-related deaths, usually appears as solitary pulmonary nodules (SPNs) which are hard to diagnose using the naked eye. In this paper, curvelet-based textural features and clinical parameters are used with three prediction models [a multilevel model, a least absolute shrinkage and selection operator (LASSO) regression method, and a support vector machine (SVM)] to improve the diagnosis of benign and malignant SPNs. Dimensionality reduction of the original curvelet-based textural features was achieved using principal component analysis. In addition, non-conditional logistical regression was used to find clinical predictors among demographic parameters and morphological features. The results showed that, combined with 11 clinical predictors, the accuracy rates using 12 principal components were higher than those using the original curvelet-based textural features. To evaluate the models, 10-fold cross validation and back substitution were applied. The results obtained, respectively, were 0.8549 and 0.9221 for the LASSO method, 0.9443 and 0.9831 for SVM, and 0.8722 and 0.9722 for the multilevel model. All in all, it was found that using curvelet-based textural features after dimensionality reduction and using clinical predictors, the highest accuracy rate was achieved with SVM. The method may be used as an auxiliary tool to differentiate between benign and malignant SPNs in CT images.

Bond-Alternation-Induced Topological Quantum Gaussian Transition and Topological Quantum Crossover in Ising Chains with the Dzyaloshinskii-Moriya Interaction

Wang Hai Tao,Cho Sam Young 한국물리학회 2020 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.77 No.12

Non-local orders, entanglement entropy, and quantum fidelity are investigated in an infinite-size bond-alternating Ising chain with the Dzyaloshinskii-Moriya interaction by employing the infinite matrix product state representation with the infinite time evolving block decimation method. Directly computing two distinct types of finite string correlations for very large lattice distances, in contrast to an extrapolated extreme value for finite size chains, reveals two topologically ordered phases. As the bond alternation varies, a topological quantum phase transition with continuously variable critical exponents along the phase boundary occurs between the two Haldane phases for a Dzyaloshinskii-Moriya interaction stronger than the Ising interaction while a topological quantum crossover between them happens through an intermediate antiferromagentic phase demonstrated with the quantum fidelity for a Dzyaloshinskii-Moriya interaction weaker than the Ising interaction. The critical exponents of the order parameters and the central charges from the entanglement entropy quantify the universality classes of the phase transition points. Anisotropic Heisenberg types of spin chains with bond alternations are finally discussed to share the same criticality.

Stress intensity factors for double-edged cracked steel beams strengthened with CFRP plates

Hai-Tao Wang,Gang Wu,Yu-Yang Pang,Habeeb M. Zakari 국제구조공학회 2019 Steel and Composite Structures, An International J Vol.33 No.5

This paper presents a theoretical and finite element (FE) study on the stress intensity factors of double-edged cracked steel beams strengthened with carbon fiber reinforced polymer (CFRP) plates. By simplifying the tension flange of the steel beam using a steel plate in tension, the solutions obtained for the stress intensity factors of the double-edged cracked steel plate strengthened with CFRP plates were used to evaluate those of the steel beam specimens. The correction factor <i>α</i>₁ was modified based on the transformed section method, and an additional correction factor <i>φ</i> was introduced into the expressions. Threedimensional FE modeling was conducted to calculate the stress intensity factors. Numerous combinations of the specimen geometry, crack length, CFRP thickness and Young's modulus, adhesive thickness and shear modulus were analyzed. The numerical results were used to investigate the variations in the stress intensity factor and the additional correction factor <i>φ</i>. The proposed expressions are a function of applied stress, crack length, the ratio between the crack length and half the width of the tension flange, the stiffness ratio between the CFRP plate and tension flange, adhesive shear modulus and thickness. Finally, the proposed expressions were verified by comparing the theoretical and numerical results.

Quantum-interference-induced Magnetization in Mesoscopic Loop Interferometers

Hai Tao Wang,Sam Young Cho,Taeseung Choi 한국물리학회 2013 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.63 No.10

We theoretically investigate quantum interference effects in mesoscopic loop interferometers. In the absence of an Aharonov-Bohm flux, the asymmetry of the arm length of the interferometer can induce a magnetic polarization current circulating along the interferometer loop. We clarify the existing regions of magnetic polarization current in terms of the dimensionless wavevector and a parameter for the asymmetric arm lengths. The magnetic polarization current is found to have a periodic diamond structure that can be characterized by magnetic and non-magnetic diamond zones. The applied magnetic flux develops a concave diamond-shaped non-magnetic region inside the magnetic diamond zones. When the magnetic flux varies across Φ= (2n + 1)π/2, with n being an integer, the magnetic diamond zone becomes a non-magnetic diamond zone and vice versa. In addition, the unique behaviors of the transport current flowing through the interferometer are discussed in association with the magnetic polarization current circulating along the interferometer loop. Finally, the magnetic moments induced at a finite bias are shown to be sufficiently large to be observed experimentally.

Extraskeletal Ewing Sarcomas in Late Adolescence and Adults: A Study of 37 Patients

Tao, Hai-Tao,Hu, Yi,Wang, Jin-Liang,Cheng, Yao,Zhang, Xin,Wang, Huan,Zhang, Su-Jie Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.5

Background: Extraskeletal Ewing sarcoma (EES)/primitive neuroectodermal tumours (PNET) are rare soft tissue sarcomas. Prognostic factors and optimal therapy are still unconfirmed. Materials and Methods: We performed a retrospective analysis on patients to explore the clinic characteristics and prognostic factors of this rare disease. A total of 37 patients older than 15 years referred to our institute from Jan., 2002 to Jan., 2012 were reviewed. The characteristics, treatment and outcome were collected and analyzed. Results: The median age was 28 years (range 15-65); the median size of primary tumours was 8.2 cm (range 2-19). Sixteen patients (43%) had metastatic disease at the initial presentation. Wide surgical margins were achieved in 14 cases (38%). Anthracycline or platinum-based chemotherapy was performed on 29 patients (74%). Radiotherapy was delivered in 13 (35%). At a median follow-up visit of 24 months (range 2-81), the media event-free survival (EFS) and overall survival (OS) were 15.8 and 30.2 months, respectively. The 3-year EFS and OS rates were 24% and 43%, respectively. Metastases at presentation and wide surgical margins were significantly associated with OS and EFS. Tumour size was significantly associated with OS but not EFS. There were no significant differences between anthracycline and platinum based chemotherapy regarding EFS and OS. Conclusions: EES/PNET is a malignant tumour with high recurrence and frequent distant metastasis. Multimodality therapy featuring wide surgical margins, aggressive chemotherapy and adjuvant local radiotherapy is necessary for this rare disease. Platinum-based chemotherapy can be used as an adjuvant therapy.

Chemical transformation and target preparation of saponins in stems and leaves of Panax notoginseng

Wang, Ru-Feng,Li, Juan,Hu, Hai-Jun,Li, Jia,Yang, Ying-Bo,Yang, Li,Wang, Zheng-Tao The Korean Society of Ginseng 2018 Journal of Ginseng Research Vol.42 No.3

Background: Notoginsenoside Ft1 is a promising potential candidate for cardiovascular and cancer disease therapy owing to its positive pharmacological activities. However, the yield of Ft1 is ultralow utilizing reported methods. Herein, an acid hydrolyzing strategy was implemented in the acquirement of rare notoginsenoside Ft1. Methods: Chemical profiles were identified by ultraperformance liquid chromatography coupled with quadruple-time-of-flight and electrospray ionization mass spectrometry (UPLC-Q/TOF-ESI-MS). The acid hydrolyzing dynamic changes of chemical compositions and the possible transformation pathways of saponins were monitored by ultrahigh-performance LC coupled with tandem MS (UHPLC-MS/ MS). Results and conclusion: Notoginsenoside Ft1 was epimerized from notoginsenoside ST4, which was generated through cleaving the carbohydrate side chains at C-20 of notoginsenosides Fa and Fc, and vinaginsenoside R7, and further converted to other compounds via hydroxylation at C-25 or hydrolysis of the carbohydrate side chains at C-3 under the acid conditions. High temperature contributed to the hydroxylation reaction at C-25 and 25% acetic acid concentration was conducive to the preparation of notoginsenoside Ft1. C-20 epimers of notoginsenoside Ft1 and ST4 were successfully separated utilizing solvent method of acetic acid solution. The theoretical preparation yield rate of notoginsenoside Ft1 was about 1.8%, which would be beneficial to further study on its bioactivities and clinical application.

Biotransformation of natural polyacetylene in red ginseng by Chaetomium globosum

Wang, Bang-Yan,Yang, Xue-Qiong,Hu, Ming,Shi, Li-Jiao,Yin, Hai-Yue,Wu, Ya-Mei,Yang, Ya-Bin,Zhou, Hao,Ding, Zhong-Tao The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.6

Background: Fermentation has been shown to improve the biological properties of plants and herbs. Specifically, fermentation causes decomposition and/or biotransformation of active metabolites into high-value products. Polyacetylenes are a class of polyketides with a pleiotropic profile of bioactivity. Methods: Column chromatography was used to isolate compounds, and extensive NMR experiments were used to determine their structures. The transformation of polyacetylene in red ginseng (RG) and the production of cazaldehyde B induced by the extract of RG were identified by TLC and HPLC analyses. Results: A new metabolite was isolated from RG fermented by Chaetomium globosum, and this new metabolite can be obtained by the biotransformation of polyacetylene in RG. Panaxytriol was found to exhibit the highest antifungal activity against C. globosum compared with other major ingredients in RG. The fungus C. globosum cultured in RG extract can metabolize panaxytriol to Metabolite A to survive, with no antifungal activity against itself. Metabolites A and B showed obvious inhibition against NO production, with ratios of 42.75 ± 1.60 and 63.95 ± 1.45% at 50 µM, respectively. A higher inhibitory rate on NO production was observed for Metabolite B than for a positive drug. Conclusion: Metabolite A is a rare example of natural polyacetylene biotransformation by microbial fermentation. This biotransformation only occurred in fermented RG. The extract of RG also stimulated the production of a new natural product, cazaldehyde B, from C. globosum. The lactone in Metabolite A can decrease the cytotoxicity, which was deemed to be the intrinsic activity of polyacetylene in ginseng.

Feedback Linearization Control of Chaos Synchronization in Coupled Map-Based Neurons Under External Electrical Stimulation

Hai-Tao Yu,Yiu Kwong Wong,Wai Lok Chan,Kai Ming Tsang,Jiang Wang 제어·로봇·시스템학회 2011 International Journal of Control, Automation, and Vol.9 No.5

In this paper, the dynamics of single and two electrically coupled map-based neurons under external electrical stimulation is studied. In order to realize the synchronization of two chaotic spiking neurons, a controller based on the idea of feedback linearization is proposed. The simulation results demonstrate the effectiveness of this developed control method. An important feature of the feedback control is that the amplitude of control signal tends to zero as soon as the synchronization is achieved.

Application of Human Papillomavirus in Screening for Cervical Cancer and Precancerous Lesions

Wang, Jin-Liang,Yang, Yi-Zhuo,Dong, Wei-Wei,Sun, Jing,Tao, Hai-Tao,Li, Rui-Xin,Hu, Yi Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.5

Cervical cancer is a commonly-encountered malignant tumor in women. Cervical screening is particularly important due to early symptoms being deficient in specificity. The main purpose of the study is to assess the application value of cervical thinprep cytologic test (TCT) and human papillomavirus (HPV) detection in screening for cervical cancer and precancerous lesions. In the study, cervical TCT and HPV detection were simultaneously performed on 12,500 patients selected in a gynecological clinic. Three hundred patients with positive results demonstrated by cervical TCT and/or HPV detection underwent cervical tissue biopsy under colposcopy, and pathological results were considered as the gold standard. The results revealed that 200 out of 12,500 patients were abnormal by TCT, in which 30 cases pertained to equivocal atypical squamous cells (ASCUS), 80 cases to low squamous intraepithelial lesion (LSIL), 70 cases to high squamous intraepithelial lesion (HSIL) and 20 cases to squamous cell carcinoma (SCC). With increasing pathological grade of cervical biopsy, however, TCT positive rates did not rise. Two hundred and eighty out of 12,500 patients were detected as positive for HPV infection, in which 50 cases were chronic cervicitis and squamous metaplasia, 70 cases cervical intraepithelial neoplasia (CIN) I, 60 cases CIN II, 70 cases CIN III and 30 cases invasive cervical carcinoma. Two hundred and thirty patients with high-risk HPV infection were detected. With increase in pathological grade, the positive rate of high-risk HPV also rose. The detection rates of HPV detection to CIN III and invasive cervical carcinoma as well as the total detection rate of lesions were significantly higher than that of TCT. Hence, HPV detection is a better method for screening of cervical cancer at present.