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        Laser-activatable Oxygen Self-supplying Nanoplatform for Efficiently Overcoming Colorectal Cancer Resistance by Enhanced Ferroptosis and Alleviated Hypoxic Microenvironment

        Hao Jiang,Hailong Tian,Zhihan Wang,Bowen Li,Rui Chen,Kangjia Luo,Shuaijun Lu,Edouard C. Nice,Wei Zhang,Canhua Huang,Yuping Zhou,Shaojiang Zheng,Feng Gao 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

        Background Colorectal cancer (CRC) is the second most deadly cancer worldwide, with chemo-resistance remaining a major obstacle in CRC treatment. Notably, the imbalance of redox homeostasis-mediated ferroptosis and the modulation of hypoxic tumor microenvironment are regarded as new entry points for overcoming the chemo-resistance of CRC. Methods Inspired by this, we rationally designed a light-activatable oxygen self-supplying chemo-photothermal nanoplatform by co-assembling cisplatin (CDDP) and linoleic acid (LA)-tailored IR820 via enhanced ferroptosis against colorectal cancer chemo-resistance. In this nanoplatform, CDDP can produce hydrogen peroxide in CRC cells through a series of enzymatic reactions and subsequently release oxygen under laser-triggered photothermal to alleviate hypoxia. Additionally, the introduced LA can add exogenous unsaturated fatty acids into CRC cells, triggering ferroptosis via oxidative stress-related peroxidized lipid accumulation. Meanwhile, photothermal can efficiently boost the rate of enzymatic response and local blood flow, hence increasing the oxygen supply and oxidizing LA for enhanced ferroptosis. Results This nanoplatform exhibited excellent anti-tumor efficacy in chemo-resistant cell lines and showed potent inhibitory capability in nude mice xenograft models. Conclusions Taken together, this nanoplatform provides a promising paradigm via enhanced ferroptosis and alleviated hypoxia tumor microenvironment against CRC chemo-resistance.

      • KCI등재

        Whole Exome Sequencing in the Male Breast Cancer with Prolactinoma: A Case Report and Literature Review

        Shuai Hao,Miao Huang,Wuguo Tian,Yi Chen,Jianjie Zhao,Donglin Luo 한국유방암학회 2020 Journal of breast cancer Vol.23 No.6

        Male breast cancer (MBC) is rare and accounts for approximately 1% of all breast cancer cases worldwide. Previous studies have suggested that several factors significantly increase the risk of MBC. Prolactinoma has the highest incidence rate among patients with functional pituitary tumors. However, whether prolactinoma is involved in the onset and progression of breast cancer remains unclear. To date, there are only five case reports globally on MBC with concurrent prolactinoma. We hereby describe the first case of MBC with prolactinoma in China. We also explored the patient's genetic profile using whole exome sequencing. Our findings may help advance our understanding of the molecular pathogenesis of MBC. Further molecular analyses of such cases are warranted to improve auxiliary molecular diagnostic methods and targeted therapy for MBC.

      • EA-D p45-IgG as a Potential Biomarker for Nasopharyngeal Carcinoma Diagnosis

        Chen, Hao,Luo, Yao-Ling,Zhang, Lin,Tian, Li-Zhen,Feng, Zhi-Ting,Liu, Wan-Li Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

        Aim: To identify new biomarkers for NPC diagnosis with an anti-EBV Western blot test kit. Methods: Serum samples from 64 NPC patients and healthy subjects with four specific VCA-IgA/EA-IgA profiles were tested with an anti-EBV Western blot test kit from EUROIMMUN AG. Proteins were quantified with scores of intensity visually assigned to the protein bands. The markers which showed statistical differences between the NPC and non-NPC subjects were further evaluated in another 32 NPC patients and 32 controls in comparison with established biomarkers including VCA-IgA, EA-IgA, EBV-related protein IgG, and EBV DNA. Results: Among the markers screened, EA-D p45-IgG showed a statistically significant difference (p < 0.05) between NPC and non-NPC subjects with VCA-IgA positivy. In 32 VCA-IgA positive NPC patients and 32 control subjects, the diagnostic accuracy of EA-D p45-IgG was 78.1% with a positive predictive value of 77.8% and a negative predictive value of 78.6%. In the verification experiment, the specificity and sensitivity of EA-D p45-IgG were 75.0% and 90.6 %, respectively. Conclusions: EA-D p45-IgG might be a potential biomarker for NPC diagnosis, especially among VCA-IgA positive subjects.

      • KCI등재

        Analysis of Circulating Tumor DNA to Predict Neoadjuvant Therapy Effectiveness and Breast Cancer Recurrence

        Shuai Hao,Wuguo Tian,Jianjie Zhao,Yi Chen,Xiaohua Zhang,Bo Gao,Yujun He,Donglin Luo 한국유방암학회 2020 Journal of breast cancer Vol.23 No.4

        Purpose: Real-time detection and intervention can be used as potential measures to markedly decrease breast cancer mortality. Assessment of circulating tumor DNA (ctDNA) may offer great benefits for the management of breast cancer over time. However, the use of ctDNA to predict the effectiveness of neoadjuvant treatment and recurrence of breast cancer has rarely been studied. Methods: We prospectively recruited 31 breast cancer patients with 4 subtypes. Three time points were set in this study, including before any therapy (C1), during surgery (T), and six months after surgery (C2). We collected peripheral blood samples from all 31 patients at C1, tumor tissue from all 31 patients at T, and peripheral blood samples from 25 patients at C2. Targeted 727-gene panel sequencing was performed on ctDNA from all blood samples and tissue DNA from all tissue samples. Somatic mutations were detected and analyzed using a reference standard pipeline. Statistical analysis was performed to identify possible associations between ctDNA profiles and clinical outcomes. Results: In total, we detected 159, 271, and 70 somatic mutations in 30 C1 samples, 31 T samples, and 12 C2 samples, respectively. We identified specific genes, such as PIK3CA, TP53, and KMT2C, which were highly mutated in the tissue samples. Furthermore, mutated KMT2C observed in ctDNA of the C2 samples may be an indicator of breast cancer recurrence. Conclusion: Our study highlights the potential of ctDNA analysis at different timepoints for assessing tumor progression and treatment effectiveness, as well as prediction of breast cancer recurrence.

      • KCI등재

        Chemical constituents from the aerial parts of Melandrium firmum

        Chang Hao Zhang,Gao Li,Jie Luo,Tian Li,Yong Cui,Mei Jin,Da Lei Yao,Ming Shan Zheng,Zhen-Hua Lin,Jiong Mo Cui 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.10

        Two new anthraquinones, melrubiellin C (1) andmelrubiellin D (2), were isolated from the aerial parts of Melandriumfirmum Rohrbach, together with eight known compounds(3–10). The structures of these compounds wereelucidated using 1Dand 2DNMR(COSY,HMQC,HMBCandNOESY) experiments. All isolated compounds were tested fortheir cytotoxicity against NCI-H460, Hep G2, MKN-28 andA-549 cells.Of these 10 compounds,1 and 2 exhibitedmoderatecytotoxicity with IC50 values ranging from 9.54 to 32.41 lM.

      • KCI등재

        Sodium tanshinone IIA sulfonate attenuates angiotensin II-induced collagen type I expression in cardiac fibroblasts in vitro

        Le Yang,Xiao-Jing Zou,Xiang Gao,Hao Chen,Jin-Long Luo,Zhao-Hua Wang,Qian-Sheng Liang,Guang-Tian Yang 생화학분자생물학회 2009 Experimental and molecular medicine Vol.41 No.7

        Cardiac fibrosis occurs after pathological stimuli to the cardiovascular system. One of the most important factors that contribute to cardiac fibrosis is angiotensin II (Ang II). Accumulating studies have suggested that reactive oxygen species (ROS) plays an important role in cardiac fibrosis and sodium tanshinone IIA sulfonate (STS) possesses antioxidant action. We therefore examined whether STS depresses Ang II-induced collagen type I expression in cardiac fibroblasts. In this study, Ang II significantly enhanced collagen type I expression and collagen synthesis. Meanwhile, Ang II depressed matrix metalloproteinase- 1 (MMP-1) expression and activity. These responses were attenuated by STS. Furthermore, STS depressed the intracellular generation of ROS, NADPH oxidase activity and subunit p47phox expression. In addition, N-acetylcysteine the ROS scavenger, depressed effects of Ang II in a manner similar to STS. In conclusion, the current studies demonstrate that anti-fibrotic effects of STS are mediated by interfering with the modulation of ROS. Cardiac fibrosis occurs after pathological stimuli to the cardiovascular system. One of the most important factors that contribute to cardiac fibrosis is angiotensin II (Ang II). Accumulating studies have suggested that reactive oxygen species (ROS) plays an important role in cardiac fibrosis and sodium tanshinone IIA sulfonate (STS) possesses antioxidant action. We therefore examined whether STS depresses Ang II-induced collagen type I expression in cardiac fibroblasts. In this study, Ang II significantly enhanced collagen type I expression and collagen synthesis. Meanwhile, Ang II depressed matrix metalloproteinase- 1 (MMP-1) expression and activity. These responses were attenuated by STS. Furthermore, STS depressed the intracellular generation of ROS, NADPH oxidase activity and subunit p47phox expression. In addition, N-acetylcysteine the ROS scavenger, depressed effects of Ang II in a manner similar to STS. In conclusion, the current studies demonstrate that anti-fibrotic effects of STS are mediated by interfering with the modulation of ROS.

      • KCI등재

        Triterpenoid saponins from Clinopodium chinense (Benth.) O. Kuntze and their biological activity

        Yin-Di Zhu,Jing-Yi Hong,Feng-Da Bao,Na Xing,Ling-Tian Wang,Zhong-Hao Sun,Yun Luo,Hai Jiang,Xudong Xu,Nai-Liang Zhu,Hai-Feng Wu,Gui-Bo Sun,Jun-Shan Yang 대한약학회 2018 Archives of Pharmacal Research Vol.41 No.12

        Four new ursane-type triterpenoid saponins, clinopoursaponins A–D (1–4), six new oleanane-type triterpenoid saponins, clinopodiside VII–XII (5–10), as well as eight known triterpene analogues (11–18), were isolated from the aerial parts of Clinopodium chinense (Benth.) O. Kuntze. The structures of the new compounds were determined based on extensive spectral analyses, including 1D (1H and 13C) and 2D NMR experiments (COSY, NOESY, HSQC, 2D TOCSY, HSQC-TOCSY and HMBC), HR-ESI-MS and chemical methods. Compounds 1–18 were evaluated for their protective effects against anoxia/reoxygenation-induced apoptosis in H9c2 cells and cytotoxicities against murine mammary carcinoma cell line 4T1. Compounds 8, 9 and 18 exhibited significant protective effects, while compound 1 exhibited cytotoxic activity with IC50 value of 7.4 μm compared to 7.6 μm for the positive control 10-hydroxycamptothecin.

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