A hemoglobin-based oxygen-carrying biomimetic nanosystem for enhanced chemo-phototherapy and hypoxia alleviation of hepatocellular carcinoma

Jing-Qing Le,Fang Yang,Xun-Huan Song,Ke-Ke Feng,Ling-Wu Tong,Meng-Die Yin,Wen-Zhong Zhang,Ying-Qi Lin,Hui Wu,Jing-Wei Shao 한국공업화학회 2023 Journal of Industrial and Engineering Chemistry Vol.123 No.-

Tumor microenvironment is characterized by low pH, high reactive oxygen species and hypoxia, whichprovides a suitable environment for cancer growth. The hypoxia not only elevates tumor angiogenesisand metastasis, but also is responsible for the development of treatment resistance, which graduallybecomes a significant impediment for cancer therapy. Therefore, we developed a biomimetic nanosystemcontaining hemoglobin extracted from red blood cells, chemotherapy drug sorafenib, sensitizer ursolicacid and photosensitizer indocyanine green for enhanced chemo-photo combination therapy of hepatocellularcarcinoma, which could not only enhance the chemotherapy effect of sorafenib bowing to thesensitizing effect of ursolic acid, but also achieved synergetic phototherapy in virtue of indocyaninegreen. Besides, the nanoparticles could effectively delivery exogenous oxygen to tumor site and amelioratethe tumor hypoxic environment with the assistance of hemoglobin. The dual-sensitization drugdelivery system was expected to effectively reduce the resistance of traditional treatment methodsagainst tumor hypoxia, providing a novel prospect for the synergistic hepatocellular carcinomatreatment.

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.

Simultaneous treatment with sorafenib and glucose restriction inhibits hepatocellular carcinoma in vitro and in vivo by impairing SIAH1-mediated mitophagy

Zhou Jing,Feng Ji,Wu Yong,Dai Hui-Qi,Zhu Guang-Zhi,Chen Pan-Hong,Wang Li-Ming,Lu Guang,Liao Xi-Wen,Lu Pei-Zhi,Su Wen-Jing,Hooi Shing Chuan,Ye Xin-Pin,Shen Han-Ming,Peng Tao,Lu Guo-Dong 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Transarterial chemoembolization (TACE) is the first-line treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). It is of high clinical significance to explore the synergistic effect of TACE with antiangiogenic inhibitors and the molecular mechanisms involved. This study determined that glucose, but not other analyzed nutrients, offered significant protection against cell death induced by sorafenib, as indicated by glucose deprivation sensitizing cells to sorafenib-induced cell death. Next, this synergistic effect was found to be specific to sorafenib, not to lenvatinib or the chemotherapeutic drugs cisplatin and doxorubicin. Mechanistically, sorafenib-induced mitophagy, as indicated by PINK1 accumulation, increased the phospho-poly-ubiquitination modification, accelerated mitochondrial membrane protein and mitochondrial DNA degradation, and increased the amount of mitochondrion-localized mKeima-Red engulfed by lysosomes. Among several E3 ubiquitin ligases tested, SIAH1 was found to be essential for inducing mitophagy; that is, SIAH1 silencing markedly repressed mitophagy and sensitized cells to sorafenib-induced death. Notably, the combined treatment of glucose restriction and sorafenib abolished ATP generation and mitophagy, which led to a high cell death rate. Oligomycin and antimycin, inhibitors of electron transport chain complexes, mimicked the synergistic effect of sorafenib with glucose restriction to promote cell death mediated via mitophagy inhibition. Finally, inhibition of the glucose transporter by canagliflozin (a clinically available drug used for type-II diabetes) effectively synergized with sorafenib to induce HCC cell death in vitro and to inhibit xenograft tumor growth in vivo. This study demonstrates that simultaneous treatment with sorafenib and glucose restriction is an effective approach to treat HCC, suggesting a promising combination strategy such as transarterial sorafenib-embolization (TASE) for the treatment of unresectable HCC.

Preferential Induction of CYP1A1 over CYP1B1 in Human Breast Cancer MCF-7 Cells after Exposure to Berberine

Wen, Chun-Jie,Wu, Lan-Xiang,Fu, Li-Juan,Shen, Dong-Ya,Zhang, Xue,Zhang, Yi-Wen,Yu, Jing,Zhou, Hong-Hao Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

Estrogens are considered the major breast cancer risk factor, and the carcinogenic potential of estrogens might be attributed to DNA modification caused by derivatives formed during metabolism. $17{\beta}$-estradiol ($E_2$), the main steroidal estrogen present in women, is metabolized via two major pathways: formation of 2-hydroxyestradiol (2-OH $E_2$) and 4-hydroxyestradiol ($4-OH\;E_2$) through the action of cytochrome P450 (CYP) 1A1 and 1B1, respectively. Previous reports suggested that $2-OH\;E_2$ has putative protective effects, while $4-OH\;E_2$ is genotoxic and has potent carcinogenic activity. Thus, the ratio of $2-OH\;E_2/4-OH\;E_2$ is a critical determinant of the toxicity of $E_2$ in mammary cells. In the present study, we investigated the effects of berberine on the expression profile of the estrogen metabolizing enzymes CYP1A1 and CYP1B1 in breast cancer MCF-7 cells. Berberine treatment produced significant induction of both forms at the level of mRNA expression, but with increased doses produced 16~ to 52~fold greater induction of CYP1A1 mRNA over CYP1B1 mRNA. Furthermore, berberine dramatically increased CYP1A1 protein levels but did not influence CYP1B1 protein levels in MCF-7 cells. In conclusion, we present the first report to show that berberine may provide protection against breast cancer by altering the ratio of CYP1A1/CYP1B1, could redirect $E_2$ metabolism in a more protective pathway in breast cancer MCF-7 cells.

Analysis on the Characteristics and Prognosis of Pulmonary Neuroendocrine Tumors

Wu, Bai-Shou,Hu, Yi,Sun, Jing,Wang, Jin-Liang,Wang, Peng,Dong, Wei-Wei,Tao, Hai-Tao,Gao, Wen-Juan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.5

Objective: To retrospectively review the clinical characteristics and analyze the prognostic factors of Chinese patients with pulmonary neuroendocrine tumors. Materials and Methods: The clinical data of 176 patients with pulmonary neuroendocrine tumors in Chinese PLA General Hospital from Mar., 2000 to Oct., 2012 were retrospectively analyzed. The parameters were evaluated by univariate and multivariate analysis, including the gender, age, smoking history, family history, TNM staging, localization (central or peripheral), tumor size, nodal status, histological subtype and treatment (operation or non-operation). Results: There were 23 patients with typical carcinoids (TC) (13.1%), 41 with atypical carcinoids (AC) (23.3%), 10 with large cell neuroendocrine carcinoma (LCNEC) (5.7%) and 102 with small cell lung cancer (SCLC) (57.9%). The median follow-up time was 64.5 months for AC, 38 months for LCNEC and 27 months for SCLC. The typical carcinoid censored data was 18 (more than 50% of the patients), so the median follow-up time was not obtained, and actuarial 5-year survivals for TC, AC, LCNEC and SCLC were 75.1%, 51.7%, 26.7% and 38.8%, respectively. COX univariate analysis revealed that the age (P=0.001), histological subtype (P=0.005), nodal status (P=0.000), treatment (P=0.000) and TNM staging (P=0.000) were the prognostic factors of the patients with pulmonary neuroendocrine tumors, whereas its multivariate analysis showed that only the age(P=0.001), TNM staging (P=0.002) and treatment (P=0.000) were independent prognostic factors. Conclusions: Radical surgery remains the treatment of choice, and is the only curative option. The age, TNM staging and treatment are confirmed to be the independent prognostic factors in multivariable models for pulmonary neuroendocrine tumors.

Genomic Screening for Targets Regulated by Berberine in Breast Cancer Cells

Wen, Chun-Jie,Wu, Lan-Xiang,Fu, Li-Juan,Yu, Jing,Zhang, Yi-Wen,Zhang, Xue,Zhou, Hong-Hao Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.10

Berberine, a common isoquinoline alkaloid, has been shown to possess anti-cancer activities. However, the underlying molecular mechanisms are still not completely understood. In the current study, we investigated the effects of berberine on cell growth, colony formation, cell cycle distribution, and whether it improved the anticancer efficiency of cisplatin and doxorubicin in human breast cancer estrogen receptor positive (ER+) MCF-7 cells and estrogen receptor negative (ER-) MDA-MB-231 cells. Notably, berberine treatment significantly inhibited cell growth and colony formation in the two cell lines, berberine in combination with cisplatin exerting synergistic growth inhibitory effects. Accompanied by decreased growth, berberine induced G1 phase arrest in MCF-7 but not MDA-MB-231 cells. To provide a more detailed understanding of the mechanisms of action of berberine, we performed genome-wide expression profiling of berberine-treated cells using cDNA microarrays. This revealed that there were 3,397 and 2,706 genes regulated by berberine in MCF-7 and MDA-MB-231 cells, respectively. Fene oncology (GO) analysis identified that many of the target genes were involved in regulation of the cell cycle, cell migration, apoptosis, and drug responses. To confirm the microarray data, qPCR analysis was conducted for 10 selected genes based on previously reported associations with breast cancer and GO analysis. In conclusion, berberine exhibits inhibitory effects on breast cancer cells proliferation, which is likely mediated by alteration of gene expression profiles.

Comparative Study of Bioactive Constituents in Crude and Processed Glycyrrhizae radix and Their Respective Metabolic Profiles in Gastrointestinal Tract In Vitro by HPLC-DAD and HPLC-ESI/MS Analyses

Wen-wu Huang,Xiaobo Li,Meng Yue Wang,Hai-ming Shi,Ying Peng,Chong-sheng Peng,Min Zhang,Yue Li,Jing Lu 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.11

Two HPLC methods with diode array detection (HPLC-DAD) and electrospray ionization-mass spectrometry (HPLC-ESI/MS), respectively, were developed to investigate the differences of chemical constituents and their metabolism in gastrointestinal tract in vitro between two decoctions of crude and processed Glycyrrhizae radix. Total of eleven constituents (liquiritin apioside, liquiritin, licuraside, isoliquiritin, ononin, glycyrrhizin, liquiritigenin-7,4'-diglucoside, licorice saponin A3, 22β-acetoxylglycyrrhizic acid, licorice saponin G2, and yunganoside E2) were identified in the two decoctions, whereas lower contents of these constituents were usually found in the decoction of processed G. radix. Furthermore, these constituents were metabolized into their respective aglycons in human intestinal bacteria juice, and the metabolism ratios were all higher in processed G. radix decoction. No change was found in artificial gastric or intestinal juice. This study revealed that the processing can alter the contents of main constituents in crude G. radix and their metabolism in gastrointestinal tract, in which intestinal bacteria play an important role in the metabolism of licorice constituents.

Selecting and Identifying Lactic Acid Bacteria in Sourdough and Their Effect on Sourdough Physical and Chemical Properties

( Jing Han Huang ),( Syue Fong Lai ),( Wen Fu Wu ),( Chen Wei Huang ),( Ying Chen Lu ) 한국농업기계학회 2018 한국농업기계학회 학술발표논문집 Vol.23 No.1

Sourdough is traditionally used as the leavening agent for bread making and a potential source of probiotics. In this study, sourdoughs from seven restaurants in Taiwan were collected. The lactic acid bacteria strains were isolated and identified by 16S rDNA sequencing from these sourdoughs. The following lactic acid bacteria species were identified: Lactobacillus pentosus, Lactobacillus paracasei, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus sanfranciscensis. Five lactic acid bacteria strains, Lactobacillus paracasei LYC1242, Lactobacillus casei LYC1244, Lactobacillus plantarum LYC1245 and Lactobacillus casei LYC1246, were selected and singly used to ferment wheat flour. The pH value of various sourdoughs decreased to pH3 from pH5 and kelp at pH3. The titratable acidity and viscosity of various sourdoughs increased significantly compared to spontaneous fermented flour. However, there is no significant difference in titratable acidity between various sourdoughs. The sourdough fermented with L. casei LYC1244 had highest cell count. These studies provided preliminary results for choosing the best lactic acid bacteria starter strain to develop probiotic sourdough bread.

High Resolution Melting Analysis for Epidermal Growth Factor Receptor Mutations in Formalin-fixed Paraffin-embedded Tissue and Plasma Free DNA from Non-small Cell Lung Cancer Patients

Jing, Chang-Wen,Wang, Zhuo,Cao, Hai-Xia,Ma, Rong,Wu, Jian-Zhong Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Background:The aim of the research was to explore a cost effective, fast, easy to perform, and sensitive method for epidermal growth factor receptor (EGFR) mutation testing. Methods: High resolution melting analysis (HRM) was introduced to evaluate the efficacy of the analysis for dectecting EGFR mutations in exons 18 to 21 using formalin-fixed paraffin-embedded (FFPE) tissues and plasma free DNA from 120 patients. Results: The total EGFR mutation rate was 37.5% (45/120) detected by direct sequencing. There were 48 mutations in 120 FFPE tissues assessed by HRM. For plasma free DNA, the EGFR mutation rate was 25.8% (31/120). The sensitivity of HRM assays in FFPE samples was 100% by HRM. There was a low false-positive mutation rate but a high false-negative rate in plasma free DNA detected by HRM. Conclusions: Our results show that HRM analysis has the advantage of small tumor sample need. HRM applied with plasma free DNA showed a high false-negative rate but a low false-positive rate. Further research into appropriate methods and analysis needs to be performed before HRM for plasma free DNA could be accepted as an option in diagnostic or screening settings.

폴리(스티렌-이소부틸렌-스티렌) 삼중블록 공중합체의 합성, 분석 및 혈액적합성

Wen Li Guo,Ping Ren,Yi Bo Wu,Shu Xin Li,Jing Mao,Fei Xiao,Kang Li 한국고분자학회 2011 폴리머 Vol.35 No.1

The synthesis of well-defined poly(styrene-b-isobutylene-b-styrene) (SIBS) triblock copolymers was accomplished by cationic sequential block copolymerization of isobutylene (IB) with styrene (St) using 1,4-di(2-chloro-2-propyl)benzene (DCC)/TiCl4 /2,6-di-tert-butylpyridine(DtBP) as an initiating system in methyl chloride (CH3Cl)/methylcyclohexane(MeChx) (50/50 v/v) solvent mixture at -80 ℃. The triblock copolymers exhibited excellent thermoplastic and elastomeric characteristics. Tensile strengths and Shore hardness increased with increasing polystyrene (PS) content, while elongation at break decreased. The blood-compatibility of SIBS was assessed by SEM observation of the platelet adhesion, blood clotting time and haemolysis ratio. The haemolysis ratios were below 5% which met the medical materials standard. The platelet adhesion test further indicated that SIBS block copolymers had a good blood compatibility.