Therapeutic Regimens and Prognostic Factors of Brain Metastatic Cancers

Song, Wen-Guang,Wang, Yi-Feng,Wang, Rui-Lin,Qu, Yin-E,Zhang, Zhi,Li, Guo-Zhong,Xiao, Ying,Fang, Fang,Chen, Hong Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.2

Objective: This work aims to investigate the therapeutic regimen of brain metastatic cancers and the relationship between clinical features and prognosis. Methods: Clinical data of 184 patients with brain metastatic cancers were collected and analysed for the relationship between survival time and age, gender, primary diseases, quantity of brain metastatic foci, their position, extra cranial lesions, and therapeutic regimens. Results: The average age of onset was 59.1 years old. The median survival time (MST) was 15.0 months, and the patients with breast cancer as the primary disease had the longest survival time. Females had a longer survival time than males. Patients with meningeal metastasis had extremely short survival time. Those with less than 3 brain metastatic foci survived longer than patients with more than 3. The MST of patients receiving radiotherapy only and the patients receiving chemotherapy only were all 10.0 months while the MST of patients receiving combination therapy was 16.0 months. Multiple COX regression analysis demonstrated that gender, primary diseases, and quantity of brain metastatic foci were independent prognostic factors for brain metastatic cancers. Conclusions: Chemotherapy is as important as radiotherapy in the treatment of brain metastatic cancer. Combination therapy is the best treatment mode. Male gender, brain metastatic cancers originating in the gastrointestinal tract, more than 3 metastatic foci, and involvement of meninges indicate a worse prognosis.

β-Lapachone suppresses radiation-induced activation of nuclear factor-κB

Guang-Zhi Dong,Eun-Taex Oh,Hyemi Lee,Moon-Taek Park,Chang Won Song,박헌주 생화학분자생물학회 2010 Experimental and molecular medicine Vol.42 No.5

Anticancer effects of β-lapachone (β-lap) are due to generation of ROS and metabolic catastrophes as a result of NAD(P)H:quinone oxidoreductase (NQO1)-mediated futile cycling between the oxidized and reduced forms of β-lap. It has been shown that NQO1 is also essential for the TNF-induced activation of NF-κB and that β-lap suppresses the TNF-induced NF-κB activation. We investigated whether or not NQO1 is involved and β-lap suppresses the radiation-induced NF-κB activation using A549 human lung cancer cells and NQO1-knock down A549 cells (shNQO1 A549cells). Irradiation with 4 Gy markedly increased the DNA binding activity of NF-κB in A549 cells, but not in the shNQO1 A549 cells, thus demonstrating that NQO1plays a pivotal role in irradiation-induced NF-κB activation. Treatment with 10 μM β-lap for 4 h almost completely abrogated the radiation-induced increase in NF-κB activation and the transcription of NF-κB target genes such as bcl2, gadd45β and cyclinD1. Moreover, β-lap markedly suppressed the activation of IκB kinase γ (IKKγ) and the subsequent phosphorylation of IκBα, thereby inhibiting NF-κB activation. It is concluded that β-lap suppresses the radiation-induced activation of NF-κB by interrupting the involvement of NQO1 in the activation of NF-κB, thereby inhibiting the transcription of survival signals. The radiosensitization caused by β-lap may, in part, be attributed to β-lap-induced suppression of NF-κB activation.

Multiconsensus of Second Order Multiagent Systems with Directed Topologies

Guang-Song Han,Zhi-Hong Guan,Xin-Ming Cheng,Yonghong Wu,Feng Liu 제어·로봇·시스템학회 2013 International Journal of Control, Automation, and Vol.11 No.6

A novel multiconsensus problem is introduced in multiagent systems. The states of multiple agents in each subnetwork asymptotically converge to a consistent value with information exchanges among subnetworks. The multiconsensus problem of second order multiagent systems with directed topologies is studied. Three linear protocols are proposed to solve the multiconsensus problem. Necessary and sufficient conditions are derived based on matrix theory. Simulations are provided to demonstrate the effectiveness of the theoretical results.

Nomogram for predicting overall survival in children with neuroblastoma based on SEER database

Song-Wu Liang,Gang Chen,Yi-Ge Luo,Peng Chen,Jin-Han Gu,Qiong-Qian Xu,Yi-Wu Dang,Li-Ting Qin,Hui-Ping Lu,Wen-Ting Huang,Zhi-Guang Huang,Li Gao,Jia-Bo Chen 대한외과학회 2020 Annals of Surgical Treatment and Research(ASRT) Vol.99 No.2

Purpose: This study was performed to establish and validate a nomogram for predicting the overall survival in children with neuroblastoma. Methods: The latest clinical data of neuroblastoma in Surveillance, Epidemiology, and End Results (SEER) database was extracted from 2000 to 2016. The cases included were randomly divided into training and validation cohorts. The survival curves were drawn with a Kaplan-Meier estimator to investigate the influences of certain single factors on overall survival. Also, least absolute shrinkage and selection operator regression was applied to further select the prognostic variables for neuroblastoma. Additionally, receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the accuracy of the nomogram. Results: In total, 1,262 patients were collected and 8 independent prognostic factors were achieved, including patients’ age, sex, race, tumor grade, radiotherapy, chemotherapy, tumor site, and tumor size. Then we constructed a nomogram by using the data of the training cohort with 886 cases. Subsequently, the nomogram was validated internally and externally with 886 and 376 cases, respectively. The internal validation revealed that the area under the curves (AUC) of ROC curves of 1-, 3-, and 5-year overall survival were 0.69, 0.78, and 0.81, respectively. Accordingly, the external validation also showed that the AUC of 1-, 3-, and 5-year overall survival were all ≥0.69. Both methods of validation demonstrated that the predictive calibration curves were consistent with standard curves. Conclusion: The nomogram possess the potential to be a new tool in predicting the survival rate of neuroblastoma patients.

Efficacy and Safety of Autologous Fibroblast (FB) Seeded Biodegradable Scaffold for Rabbit Penile Girth Enlargement

( Yi Guang Wu ),( Zhe Jin ),( Zhong Cheng Xin ),( Wei Dong Song ),( Jing Peng ),( Zhi Chao Zhang ),( Bing Gao ),( Ze Long Kim ) 한국조직공학·재생의학회 2007 조직공학과 재생의학 Vol.4 No.4

The purpose of this experiment is to construct an in vitro model of rabbit penis enlargement using tissue engineering method, and to investigate the efficacy and safety of autologous fibroblast cell seeded to biodegradable scaffold and also to provide a new perspective of clinical application. We observed the growth of GFP transgenic fibroblast cell from SD mouse after transplantation with the biodegradable scaffold by fluorescence microscope. At the second hand, 160 male New Zealand rabbits were divided into four groups; Group A for control; Group B for acellular matrix implanted; Group C for scaffold implanted only; Group D for autologous cultured fibroblast seeded scaffold. Rabbit scrotal skin (4×4 mm) was detached under general anesthesia, and fibroblast (FB) was cultured and proliferated for 2weeks. Cultured cells were seeded into the scaffold and inserted on the between buck`s and dartos fascia of rabbit penis. To assess the efficacy and safety of the cells, we observed for 4months. The FB of rabbit were successfully cultured and confirmed by immunohistochemistry method. In the results of group D, dermal cell seeding group, the penile girth was significantly increased to 22.3% compared to other groups (Group A 0.3%, Group B 12.7%, Group C 14.6% and Group D 22.3%). We checked the results in 2~4 months later. We observed that moderate penile girth increase was gained using the biodegradable scaffold without other side-effects. Therefore, we carefully suggest a new guidance for penile augmentation by the tissue engineering method.

Inhaled Formaldehyde Induces Bone Marrow Toxicity via Oxidative Stress in Exposed Mice

Yu, Guang-Yan,Song, Xiang-Fu,Liu, Ying,Sun, Zhi-Wei Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

Formaldehyde (FA) is an economically important chemical, and has been found to cause various types of toxic damage to the body. Formaldehyde-induced toxic damage involves reactive oxygen species (ROS) that trigger subsequent toxic effects and inflammatory responses, which may increase risk of cancer. Therefore, in the present study, we aimed to investigate the possible toxic mechanism in bone marrow caused by formaldehyde. In accordance with the principle of randomization, the mice were divided into four groups of 6 mice per group. One group was exposed to ambient air and the other three groups were exposed to different concentrations of formaldehyde (20, 40, $80mg/m^3$) for 15 days in the respective inhalation chambers, 2h a day. At the end of the 15-day experimental period, all mice were killed. Bone marrow cells were obtained. Some of those were used for the determination of blood cell numbers, bone marrow karyote numbers, CFU-F, superoxide dismutase (SOD) activity and malondialdehyde (MDA) content; others were used for the determination of mitochondrial membrane potential (MMP), cell cycle and Bcl-2, Bax, CytC protein expression. WBC and PLT numbers in median and high dose groups were obvious reduced, but there was no change on RBC numbers. There was also reduced numbers of bone marrow karyotes and CFU-F in the high dose group. SOD activity was decreased, but MDA content was increased. MMP and Bcl-2 expression were decreased with increasing formaldehyde concentration, while expression of Bax and Cyt C was increased. We also observed change in cell cycling, and found that there was S phase arrest in the high dose group. Our study suggested that a certain concentration of formaldehyde could have toxic effects on the hematopoietic system, with oxidative stress as a critical effect.

Magnetic Resonance Venography Findings of Obstructed Hepatic Veins and the Inferior Vena Cava in Patients with Budd-Chiari Syndrome

Ru-Xin Song,Shi-Feng Cai,Shuang Ma,Zhi-Ling Liu,Yong-Hao Gai,Chun-Qing Zhang,Guang-Chuan Wang 대한영상의학회 2018 Korean Journal of Radiology Vol.19 No.3

Objective: This study aimed to illustrate the magnetic resonance venography (MRV) manifestations of obstructed hepatic veins (HVs), the inferior vena cava (IVC), and accessory hepatic veins (AHVs) in patients with Budd-Chiari syndrome (BCS) and to evaluate the visualization capacity of MRV in the diagnosis of BCS. Materials and Methods: Fifty-two patients with chronic BCS were included in this study. All patients were examined via MRV performed with a 3T system following injections of gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) or Gdethoxibenzyl-DTPA. HV and IVC lesions were classified, and their characteristics were described. HV cord-like occlusions detected via MRV were compared using ultrasonography (US). Digital subtraction angiography (DSA) was performed as a contrast in the MRV detection of IVC lesions. The HVs draining collaterals, mainly AHVs, were carefully observed. HV lesions were classified as segmental stenosis, segmental occlusion, membranous stenosis, membranous occlusion, cord-like occlusion, or non-visualized. Except for patent IVCs, IVC lesions were classified as segmental occlusion, segmental stenosis, membranous occlusion, membranous stenosis, and hepatomegaly-induced stenosis. Results: All patients (52/52, 100%) showed HV lesions of different degrees. MRV was inferior to US in detecting cord-like occlusions (6 vs. 19, χ2 = 11.077, p < 0.001). Dilated AHVs, including 50 (50/52, 96.2%) caudate lobe veins and 37 (37/52, 71.2%) inferior HV and AHV lesions, were well-detected. There were no significant differences in detecting segmental lesions and thrombosis between MRV and DSA (χ2 = 0.000, p1 = 1.000, p2 = 1.000). The capacity of MRV to detect membranous lesions was inferior to that of DSA (7 vs. 15, χ2 = 6.125, p = 0.013). Conclusion: In patients with BCS, MRV can clearly display the lesions in HVs and the IVC, as well as in AHVs, and it has diagnostic and therapeutic value.

Cisplatin enhances the anticancer effect of &bgr;-lapachone by upregulating NQO1

Terai, Kaoru,Dong, Guang-Zhi,Oh, Eun-Taex,Park, Moon-Taek,Gu, Yeunhwa,Song, Chang Won,Park, Heon Joo Lippincott Williams Wilkins, Inc. 2009 ANTICANCER DRUGS Vol.20 No.10

NAD(P)H:quinone oxidoreductase (NQO1) has been reported to play an important role in cell death caused by &bgr;-lapachone (&bgr;-lap), 3,4-dihydro-22,2-dimethyl-2H-naphthol[1,22b]pyran-5,6-dione. This study investigated whether cisplatin (cis-diamminedichloroplatinum) sensitizes cancer cells to &bgr;-lap by upregulating NQO1. The cytotoxicity of cisplatin and &bgr;-lap alone or in combination against FSaII fibrosarcoma cells of C3H mice in vitro was determined with a clonogenic survival assay and assessment of &ggr;-H2AX foci formation, a hallmark of DNA double-strand breaks. The cellular sensitivity to &bgr;-lap progressively increased during the 24 h after cisplatin treatment. The expression and enzymatic activity of NQO1 also increased during the 24 h after cisplatin treatment, and dicoumarol, an inhibitor of NQO1, was found to nullify the cisplatin-induced increase in &bgr;-lap sensitivity. The role of NQO1 in the cell death caused by &bgr;-lap alone or in combination with cisplatin was further elucidated using NQO1-positive and NQO1-negative MDA-MB-231 human breast cancer cells. Cisplatin increased the sensitivity of the NQO1-positive but not the NQO1-negative MDA-MB-231 cells to &bgr;-lap treatment. Combined treatment with cisplatin and &bgr;-lap suppressed the growth of FSaII tumors in the legs of C3H mice in a manner greater than additive. It is concluded that cisplatin markedly increases the sensitivity of cancer to &bgr;-lap in vitro and in vivo by upregulating NQO1.

Recombinant Human Granulocyte Colony-Stimulating Factor Promotes Preinvasive and Invasive Estrogen Receptor-Positive Tumor Development in MMTV-erbB2 Mice

Chun Ling Zhao,Guang Ping Zhang,Zheng Zheng Xiao,Zhi Kun Ma,Cai Peng Lei,Shi Yuan Song,Ying Ying Feng,Ya Chao Zhao,Xiao Shan Feng 한국유방암학회 2015 Journal of breast cancer Vol.18 No.2

Purpose: We investigated whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) could promote the development of preinvasive and invasive breast cancer in mouse mammary tumor virus (MMTV-erbB2) mice with estrogen receptor- positive tumors. Methods: MMTV-erbB2 mice were randomly divided into three experimental groups with 20 mice in each group. MMTV-erbB2 mice were treated with daily subcutaneous injections of vehicle or rhG-CSF (low-rhG-CSF group, rhG-CSF 0.125 μg; vehicle-rhG-CSF group, normal saline 0.25 μg; and high-rhG-CSF group, rhG-CSF 0.25 μg) at 3 months of age. Cellular and molecular mechanisms of G-CSF action in mammary glands were investigated via immunohistochemistry and reverse transcription polymerase chain reaction. Results: Low, but not high, rhG-CSF doses significantly accelerated mammary tumorigenesis in MMTV-erbB2 mice. Short-term treatment with rhG-CSF could significantly promote the development of preinvasive mammary lesions. The cancer prevention effect was associated with reduced expression of proliferating cell nuclear antigen, cluster of differentiation 34, and signal transducers and activators of transcription 3 in mammary glands by >80%. Conclusion: We found that G-CSF was regulated by rhG-CSF both in vitro and in vivo. Identification of G-CSF genes helped us further understand the mechanism by which G-CSF promotes cancer. Low doses of rhG-CSF could significantly increase tumor latency and increase tumor multiplicity and burden. Moreover, rhG-CSF effectively promotes development of both malignant and premalignant mammary lesions in MMTV-erbB2 mice.

The interaction of serum albumin with ginsenoside Rh2 resulted in the downregulation of ginsenoside Rh2 cytotoxicity

Yingjia Lin,Yang Li,Zhi-Guang Song,Hongyan Zhu,Ying-Hua Jin 고려인삼학회 2017 Journal of Ginseng Research Vol.41 No.3

Background: Ginsenoside Rh2 (G-Rh2) is a ginseng saponin that is widely investigated because of its remarkable antitumor activity. However, the molecular mechanism by which (20S) G-Rh2 triggers its functions and how target animals avoid its cytotoxic action remains largely unknown. Methods: Phage display was used to screen the human targets of (20S) G-Rh2. Fluorescence spectroscopy and UV-visible absorption spectroscopy were used to confirm the interaction of candidate target proteins and (20S) G-Rh2. Molecular docking was utilized to calculate the estimated free energy of binding and to structurally visualize their interactions. MTT assay and immunoblotting were used to assess whether human serum albumin (HSA), bovine serum albumin (BSA), and bovine serum can reduce the cytotoxic activity of (20S) G-Rh2 in HepG2 cells. Results: In phage display, (20S) G-Rh2-beads and (20R) G-Rh2-beads were combined with numerous kinds of phages, and a total of 111 different human complementary DNAs (cDNA) were identified, including HSA which had the highest rate. The binding constant and number of binding site in the interaction between (20S)-Rh2 and HSA were 3.5 105 M1 and 1, and those in the interaction between (20S) G-Rh2 and BSA were 1.4 105 M1 and 1. The quenching mechanism is static quenching. HSA, BSA and bovine serum significantly reduced the proapoptotic effect of (20S) G-Rh2. Conclusion: HSA and BSA interact with (20S) G-Rh2. Serum inhibited the activity of (20S) G-Rh2 mainly due to the interaction between (20S) G-Rh2 and serum albumin (SA). This study proposes that HSA may enhance (20S) G-Rh2 water solubility, and thus might be used as nanoparticles in the (20S) G-Rh2 delivery process.