scholarly journals Anticolorectal Cancer Effects of AUCAN: Effects to Suppress Proliferation, Metastasis, and Invasion of Tumor Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Liu-Lin Xiong ◽  
Ruo-Lan Du ◽  
Jun-Jie Chen ◽  
Ya Jiang ◽  
Lu-Lu Xue ◽  
...  
Keyword(s):  
Side Effects ◽  
Liver Function ◽  
Clustering Analysis ◽  
Proteomic Analysis ◽  
Functional Clustering ◽  
Tumor Tissues ◽  
Hct 116 ◽  
Functional Clustering Analysis ◽  
Blood Routine

Background. Colorectal cancer (CRC) is an underlying deadly malignancy with poor prognosis, lacking effective therapies currently available to improve the prognosis. C18H17NO6 (AUCAN), a kind of dibenzofuran extracted from a special plant in Yunnan Province (China), is identified as a natural anticancer agent exerting strong inhibitory activities on various cancers. Our study was committed to investigating the potency of AUCAN against colorectal cancers and further exploring the potential mechanisms via proteomic analysis. Methods. Cell Counting Kit-8 assay and immunofluorescence staining were used to investigate the effect of AUCAN on the viability and proliferation of HCT-116 cells and RKO cells. The apoptosis of HCT-116 and RKO cells after AUCAN administration was determined by the flow cytometry test. The effects of AUCAN on invasion and migration of tumor cells were investigated by the colony formation assay, wound healing test, and Transwell invasion test. Meanwhile, the energy metabolism and growth of tumor tissues after AUCAN administration with 10 mg/kg and 20 mg/kg were examined by PET-CT in vivo. The side effects of AUCAN treatment were also evaluated through blood routine and liver function examination. RKO cell proliferation and apoptosis in vivo were further determined by hematoxylin and eosin staining, TUNEL staining, and immunohistochemistry. Furthermore, the differentially expressed proteins (DEPs) involved in AUCAN treatment were determined by proteomic analysis followed by functional clustering analysis. Results. The results showed that AUCAN suppressed the migratory abilities and enhanced apoptosis of HCT-116 and RKO cell lines. Meanwhile, AUCAN treatment dramatically depressed the growth and volume of colorectal tumors in nude mice and suppressed the survival of RKO cells in tumor tissues without any side effects on the blood routine and liver function. In addition, twenty-four upregulated and forty-two downregulated proteins were identified. Additionally, functional clustering analysis concealed enriched biological processes, cellular components, molecular functions, and related pathways of these proteins involved in cellular metabolic. Finally, the protein-protein interaction analysis revealed the regulatory connection among these DEPs. Conclusions. Taken together, AUCAN exerted its significant antitumor effect without side effects in the blood routine and liver function and the underlying mechanisms were preliminarily investigated by proteomic analysis.

scholarly journals Novel Microcrystal Formulations of Sorafenib Facilitate a Long-Acting Antitumor Effect and Relieve Treatment Side Effects as Observed With Fundus Microcirculation Imaging

2021 ◽  
Vol 11 ◽  
Author(s):  
Junxiao Wang ◽  
Rui Liu ◽  
Yun Zhao ◽  
Zhenhu Ma ◽  
Zejie Sang ◽  
...  
Keyword(s):  
Side Effects ◽  
Antitumor Effect ◽  
Kinase Inhibitors ◽  
Advanced Hepatocellular Carcinoma ◽  
Related Factors ◽  
Treatment Side Effects ◽  
Tumor Tissues ◽  
Long Acting ◽  
Medical Burden

The tyrosine kinase inhibitors (TKIs), including sorafenib, remain one first-line antitumor treatment strategy for advanced hepatocellular carcinoma (HCC). However, many problems exist with the current orally administered TKIs, creating a heavy medical burden and causing severe side effects. In this work, we prepared a novel microcrystalline formulation of sorafenib that not only achieved sustainable release and long action in HCC tumors but also relieved side effects, as demonstrated by fundus microcirculation imaging. The larger the size of the microcrystalline formulation of sorafenib particle, the slower the release rates of sorafenib from the tumor tissues. The microcrystalline formulation of sorafenib with the largest particle size was named as Sor-MS. One intratumor injection (once administration) of Sor-MS, but not Sor-Sol (the solution formulation of sorafenib as a control), could slow the release of sorafenib in HCC tumor tissues and in turn inhibited the in vivo proliferation of HCC or the expression of EMT/pro-survival–related factors in a long-acting manner. Moreover, compared with oral administration, one intratumor injection of Sor-MS not only facilitated a long-acting antitumor effect but also relieved side effects of sorafenib, avoiding damage to the capillary network of the eye fundus, as evidenced by fundus microcirculation imaging. Therefore, preparing sorafenib as a novel microcrystal formulation could facilitate a long-acting antitumor effect and relieve drug-related side effects.

scholarly journals Functional clustering analysis identifies specific subtypes of aldehyde dehydrogenase associated with glioma immunity

2021 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
Di Wang ◽  
Haoyu Jiang ◽  
Zhiliang Wang ◽  
Ruoyu Huang ◽  
Tao Jiang ◽  
...  
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Clustering Analysis ◽  
Functional Clustering ◽  
Functional Clustering Analysis

Multilevel Functional Clustering Analysis

Biometrics ◽  
2012 ◽  
Vol 68 (3) ◽  
pp. 805-814 ◽  
Author(s):  
Nicoleta Serban ◽  
Huijing Jiang
Keyword(s):  
Clustering Analysis ◽  
Functional Clustering ◽  
Functional Clustering Analysis

Hyperthermia Enhances The Effect Of Magnetic Fe3O4nanoparticle Loaded With Daunorubicin On Leukemia and Drug Accumulation In Tumor In Vivo

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5038-5038 ◽  
Author(s):  
Ran Liu ◽  
Weiwei Wu ◽  
Baoan Chen ◽  
Jian Cheng ◽  
Jun Wang ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Multidrug Resistance ◽  
Magnetic Nanoparticles ◽  
Side Effects ◽  
Prussian Blue ◽  
Tumor Volume ◽  
Fe3o4 Magnetic Nanoparticles ◽  
Xenograft Tumor ◽  
Tumor Tissues

Abstract Multidrug resistance in cancer and adverse effects of chemotherapy are the major obstacles for cancer therapeutics. This study was aimed to investigate the efficiency of novel multifunctional Fe3O4 magnetic nanoparticles combined with chemotherapeutic agents and hyperthermia in order to reverse multidrug resistance and reduce side effects by concentrating chemotherapeutics on the target site in vivo leukemia models. K562 and K562/A02 xenograft tumor-bearing nude mice were randomly divided into 4 groups, a control group and the treatment groups were allocated to receive daunorubicin (DNR), Fe3O4 magnetic nanoparticles (Fe3O4-MNP), and Fe3O4 magnetic nanoparticles loaded with daunorubicin (DNR-Fe3O4-MNP). All groups were subjected to hyperthermia in an alternating magnetic field. Tumor volume was measured with a vernier caliper. Daunorubicin concentrations in plasma, tumor and non-tumor tissues were determined by high performance liquid chromatography (HPLC). Tumor and non-tumor tissues were stained with Hematoxylin and Eosin for histopathological and microscopic examination. Locations of Fe3O4 magnetic nanoparticles in tumor tissues were stained with Prussian blue for microscope examination. In Fe3O4-MNP and DNR-Fe3O4-MNP treated groups of both K562 and K562/A02 xenograft models, tumor temperature obviously increased and tumor volume became significantly smaller.  Apoptosis was observed in tumor cells treated with  DNR-Fe3O4-MNP groups.  In all DNR-Fe3O4-MNP groups of K562 and K562/A02 xenograft tumor models, the tumor inhibition rate, daunorubicin concentration  were higher level and  daunorubicin clearance in kidney also was delayed when compared with DNR alone treated group. Location of Fe3O4 magnetic nanoparticles with Prussian blue staining showed that Fe3O4 magnetic nanoparticles could be seen in tumor tissues. No obvious histopathological damage was observed in other non-tumor tissues.  Fe3O4 magnetic nanoparticles played an important role in increasing tumor temperature during hyperthermia, and can be delivered successfully to tumor site in an alternating magnetic field. Fe3O4 magnetic nanoparticles loaded with daunorubicin with hyperthermia had the strongest inhibitory effect on tumor and would be potential approach for improving the efficacy of chemotherapeutics, reducing side effects and reversing multidrug resistance in the treatment of leukemia. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Functional clustering analysis of Chinese provincial wind power generation

2020 ◽  
pp. 014459872090917
Author(s):  
Yizheng Fu ◽  
Zhifang Su
Keyword(s):  
Power Generation ◽  
Wind Energy ◽  
Wind Power ◽  
Clustering Analysis ◽  
Energy Generation ◽  
Wind Power Generation ◽  
Monthly Data ◽  
Functional Clustering ◽  
Wind Energy Generation ◽  
Functional Clustering Analysis

China is a broad territory country. There are significant differences in the terrain, climate, and other environmental factors between different provinces, which affect wind power generation. In order to better analyze the situation of wind power generation in Chinese provinces, this paper uses the functional clustering analysis to classify the monthly data of wind power generation in 30 Chinese provinces from March 2013 to October 2019. The empirical results of this paper show that the wind energy generation in Chinese provinces can be divided into three categories, and the results are consistent with the actual situation. In this paper, functional clustering analysis is used to analyze monthly data, compared with the traditional clustering analysis to analyze annual data which are obtained by accumulated monthly data. Higher-dimensional data can be used for analysis to reduce information loss. Moreover, data can be viewed as functions, and more information can be mined by analyzing derivative functions, and so on. The analysis of wind energy generation has certain guiding significance for the development and utilization of renewable energy.

A Comparative Ex Vivo Study of Plasminogen Activators and Proteases for Fibrinolytic Activity and Side Effects in Rabbits

1977 ◽  
Vol 37 (01) ◽  
pp. 154-161 ◽  
Author(s):  
B. A Janik ◽  
S. E Papaioannou
Keyword(s):  
Side Effects ◽  
Effective Dose ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Plasminogen Activators ◽  
Assay System ◽  
Coagulation Parameters ◽  
Ex Vivo Assay

SummaryUrokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose, were administered to monitor potential toxicity revealing that Brinase, trypsin, and SN 687 were very toxic at this concentration.Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo.The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.

Acyl-Enzymes as Thrombolytic Agents in Dog Models of Venous Thrombosis and Pulmonary Embolism

1984 ◽  
Vol 51 (02) ◽  
pp. 248-253 ◽  
Author(s):  
R J Dupe ◽  
P D English ◽  
R A G Smith ◽  
J Green
Keyword(s):  
Pulmonary Embolism ◽  
Side Effects ◽  
Venous Thrombosis ◽  
Active Site ◽  
Acute Pulmonary Embolism ◽  
Quantitative Model ◽  
Beagle Dog ◽  
Thrombosis Model ◽  
Derivatives Of

SummaryA quantitative model of venous thrombosis in the beagle dog is described. The model was adapted to permit ageing of isolated experimental clots in vivo. A model of acute pulmonary embolism in this species is also described. In the venous thrombosis model, infusion of streptokinase (SK) or SK-activated human plasmin gave significant lysis but bolus doses of SK. plasmin complex were ineffective. Active site anisoylated derivatives of SK. plasminogen complex, SK-activated plasmin and activator-free plasmin were all active when given as bolus doses in both models. At lytic doses, the acyl-enzymes caused fewer side-effects attributable to plasminaemia than the corresponding unmodified enzymes.

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