scholarly journals Tetrandrine Suppresses Human Brain Glioblastoma GBM 8401/luc2 Cell-Xenografted Subcutaneous Tumors in Nude Mice In Vivo

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7105
Author(s):  
Ching-Lung Liao ◽  
Yi-Shih Ma ◽  
Te-Chun Hsia ◽  
Yu-Cheng Chou ◽  
Jin-Cherng Lien ◽  
...  
Keyword(s):  
Nude Mice ◽  
Cell Apoptosis ◽  
Imaging System ◽  
The Body ◽  
Photon Flux ◽  
Glioblastoma Cells ◽  
Group I ◽  
Wide Range ◽  
Significant Difference

Tetrandrine (TET), a bisbenzylisoquinoline (BBI) alkaloid, is isolated from the plant Stephania tetrandra S. Moore and has a wide range of biological activity, including anticancer properties in vitro and in vivo. At first, we established a luciferase-expressing stable clone that was named GBM 8401/luc2 cells. Herein, the primary results indicated that TET reduced the total cell viability and induced cell apoptosis in GBM 8401/luc2 human glioblastoma cells. However, there is no available information showing that TET suppresses glioblastoma cells in vivo. Thus, we investigated the effects and mechanisms of TET on a GBM 8401/luc2 cell-generated tumor in vivo. After the tumor volume reached 100–120 mm3 in subcutaneously xenografted nude mice, all of the mice were randomly divided into three groups: Group I was treated with phosphate-buffered solution (PBS) containing 0.1% dimethyl sulfoxide, Group II with 25 mg/kg of TET, and Group III with 50 mg/kg of TET. All mice were given the oral treatment of PBS or TET by gavage for 21 days, and the body weight and tumor volumes were recorded every 5 days. After treatment, individual tumors, kidneys, livers, and spleens were isolated from each group. The results showed that TET did not affect the body weights, but it significantly decreased the tumor volumes. The TET treatment at 50 mg/kg had a two-fold decrease in tumor volumes than that at 25 mg/kg when compared to the control. TET decreased the total photon flux, and treatment with TET at 50 mg/kg had a lower total photon flux than that at 25 mg/kg, as measured by a Xenogen IVIS imaging system. Moreover, the higher TET treatment had lower tumor volumes and weights than those of the lower dose. The apoptosis-associated protein expression in the tumor section was examined by immunohistochemical analysis, and the results showed that TET treatment reduced the levels of c-FLIP, MCL-1, and XIAP but increased the signals of cleaved-caspase-3, -8, and -9. Furthermore, the hematoxylin and eosin (H & E) staining of kidney, liver, and spleen tissues showed no significant difference between the TET-treated and control groups. Overall, these observations demonstrated that TET suppressed subcutaneous tumor growth in a nude-mice model via the induction of cell apoptosis.

scholarly journals Demethoxycurcumin Suppresses Human Brain Glioblastoma Multiforme GBM 8401 Cell Xenograft Tumor in Nude Mice In Vivo

2021 ◽  
Vol 22 (11) ◽  
pp. 5503
Author(s):  
Yi-Ping Huang ◽  
Yi-Shih Ma ◽  
Chao-Lin Kuo ◽  
Ching-Lung Liao ◽  
Po-Yuan Chen ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Tumor Volume ◽  
The Body ◽  
Photon Flux ◽  
Xenograft Tumor ◽  
Human Glioblastoma ◽  
Human Glioblastoma Multiforme ◽  
Group I ◽  
Significant Difference

Demethoxycurcumin (DMC), a derivate of curcumin, has been shown to induce apoptotic cell death in human glioblastoma multiforme GBM 8401 cells via cell cycle arrest and induction of cell apoptosis. However, there is no report showing DMC suppresses glioblastoma multiforme cells in vivo. In the present study, we investigated the effects of DMC on GBM8401 cells in vivo. At first, we established a luciferase-expressing stable clone named GBM 8401/luc2. Second, mice were inoculated subcutaneously with GBM 8401/luc2 cells to generate a xenograft tumor mice model. After inoculation, tumor volume reached 100–120 mm3, and all mice were randomly divided into three groups: Group I was treated with 110 µL phosphate-buffered solution (PBS) containing 0.1% dimethyl sulfoxide, Group II with 30 mg/kg of DMC, and Group III with 60 mg/kg of DMC. Mice from each group were given the oral treatment of DMC by gavage for 21 days. The body weight and tumor volume were recorded every 3 days. DMC significantly decreased the tumor volumes, and 60 mg/kg treatment showed a higher decrease in tumor volumes than that of 30 mg/kg, However, DMC did not affect the body weights. The photons emitted from mice tumors were detected with Xenogen IVIS imaging system, DMC at both doses decreased the total photon flux and 60 mg/kg treatment of DMC has low total photon flux than that of 30 mg/kg. The tumor volumes and weights in 60 mg/kg treatment of DMC were lower than that of 30 mg/kg. Immunohistochemical analysis was used to measure protein expression of tumors and results showed that DMC treatment led to lightly staining with anti-Bcl-2 and -XIAP and 60 mg/kg treatment of DMC has lighter staining with anti-Bcl-2 and -XIAP than that of 30 mg/kg. The higher dose (60 mg/kg) of DMC has higher signals of cleaved-caspase-3 than that of the lower dose (30 mg/kg). Furthermore, the hematoxylin and eosin (H&E) staining of liver tissues showed no significant difference between DMC-treated and control-groups. Overall, these observations showed that DMC suppressed tumor properties in vivo and DMC may be used against human glioblastoma multiforme in the future.

scholarly journals Bisdemethoxycurcumin Induces Cell Apoptosis and Inhibits Human Brain Glioblastoma GBM 8401/Luc2 Cell Xenograft Tumor in Subcutaneous Nude Mice In Vivo

2022 ◽  
Vol 23 (1) ◽  
pp. 538
Author(s):  
Te-Chun Hsia ◽  
Shu-Fen Peng ◽  
Fu-Shin Chueh ◽  
Kung-Wen Lu ◽  
Jiun-Long Yang ◽  
...  
Keyword(s):  
Nude Mice ◽  
Cell Apoptosis ◽  
Biological Activities ◽  
The Body ◽  
Cancer Drug ◽  
Control Group ◽  
Human Glioblastoma ◽  
Anticancer Effects

Bisdemethoxycurcumin (BDMC) has biological activities, including anticancer effects in vitro; however, its anticancer effects in human glioblastoma (GBM) cells have not been examined yet. This study aimed to evaluate the tumor inhibitory effect and molecular mechanism of BDMC on human GBM 8401/luc2 cells in vitro and in vivo. In vitro studies have shown that BDMC significantly reduced cell viability and induced cell apoptosis in GBM 8401/luc2 cells. Furthermore, BDMC induced apoptosis via inhibited Bcl-2 (anti-apoptotic protein) and increased Bax (pro-apoptotic proteins) and cytochrome c release in GBM 8401/luc2 cells in vitro. Then, twelve BALB/c-nude mice were xenografted with human glioblastoma GBM 8401/luc2 cancer cells subcutaneously, and the xenograft nude mice were treated without and with BDMC (30 and 60 mg/kg of BDMC treatment) every 3 days. GBM 8401/luc2 cell xenografts experiment showed that the growth of the tumors was significantly suppressed by BDMC administration at both doses based on the reduction of tumor size and weights. BDMC did not change the body weight and the H&E histopathology analysis of liver samples, indicating that BDMC did not induce systemic toxicity. Meanwhile, treatment with BDMC up-regulated the expressions of BAX and cleaved caspase-3, while it down-regulated the protein expressions of Bcl-2 and XIAP in the tumor tissues compared with the control group. This study has demonstrated that BDMC presents potent anticancer activity on the human glioblastoma GBM 8401/luc2 cell xenograft model by inducing apoptosis and inhibiting tumor cell proliferation and shows the potential for further development to the anti-GBM cancer drug.

In-vivo anti-oxidant screening of Tectona grandis extract

2020 ◽  
Vol 9 (1) ◽  
pp. 1-4
Author(s):  
Tamilarasi G P ◽  
Sabarees G
Keyword(s):  
Biochemical Parameters ◽  
Tectona Grandis ◽  
The Body ◽  
Altered Expression ◽  
Physiological Conditions ◽  
Synthetic Drugs ◽  
Significant Difference ◽  
Anti Oxidant ◽  
Radical Generation

Oxidation is an essential reaction in the human body, which determines the expression of proteins in the body. This results in the altered expression like rapid growth resulting in cancers and other disorders. Many synthetic drugs are available in the market that is effective in limiting the free radical generation and the reaction of radicals with cells. Unfortunately, all those synthetic drugs were found to cause side effects and adverse effects in the body. But given the accuracy of the predictability of the results and administration, this research focuses on testing the anti-oxidant efficiency in rat models testing the biochemical parameters. Investigations have also been done on the anti-oxidant activity of Tectona, but every research was concentrated to prove the anti-oxidant activity only. extract had been tested for anti-oxidant activity by estimating various tissue parameters and it showed better activity. As predicted, there is a significant difference in the and results which can be explained are due to the physiological conditions that exist inside the body.

scholarly journals A Tumbling Magnetic Microrobot System for Biomedical Applications

Micromachines ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 861
Author(s):  
Elizabeth E. Niedert ◽  
Chenghao Bi ◽  
Georges Adam ◽  
Elly Lambert ◽  
Luis Solorio ◽  
...  
Keyword(s):  
Ultrasound Imaging ◽  
Biomedical Applications ◽  
Imaging System ◽  
Ex Vivo ◽  
Negative Control ◽  
Circular Path ◽  
Rotational Axis ◽  
Significant Difference

A microrobot system comprising an untethered tumbling magnetic microrobot, a two-degree-of-freedom rotating permanent magnet, and an ultrasound imaging system has been developed for in vitro and in vivo biomedical applications. The microrobot tumbles end-over-end in a net forward motion due to applied magnetic torque from the rotating magnet. By turning the rotational axis of the magnet, two-dimensional directional control is possible and the microrobot was steered along various trajectories, including a circular path and P-shaped path. The microrobot is capable of moving over the unstructured terrain within a murine colon in in vitro, in situ, and in vivo conditions, as well as a porcine colon in ex vivo conditions. High-frequency ultrasound imaging allows for real-time determination of the microrobot’s position while it is optically occluded by animal tissue. When coated with a fluorescein payload, the microrobot was shown to release the majority of the payload over a 1-h time period in phosphate-buffered saline. Cytotoxicity tests demonstrated that the microrobot’s constituent materials, SU-8 and polydimethylsiloxane (PDMS), did not show a statistically significant difference in toxicity to murine fibroblasts from the negative control, even when the materials were doped with magnetic neodymium microparticles. The microrobot system’s capabilities make it promising for targeted drug delivery and other in vivo biomedical applications.

scholarly journals Comparison between Vinorelbine–Carboplatin and Vinorelbine–Cisplatin in Stage III–IV EGFR Mutations-Negative NSCLC

2021 ◽  
Author(s):  
Laksmi Wulandari ◽  
Gatot Soegiarto ◽  
Anna Febriani ◽  
Farah Fatmawati ◽  
Wirya Sastra Amran
Keyword(s):  
Lung Cancer ◽  
Body Weight ◽  
Evaluation Criteria ◽  
Growth Factor Receptor ◽  
The Body ◽  
Stage Iii ◽  
Egfr Mutations ◽  
Group I ◽  
Significant Difference ◽  
Group Ii

Abstract Introduction There are a substantial number of lung cancer patients with negative mutations in Indonesia. This type of cancer is deemed to be the major contributor of lung cancer patient’s death. However, reseaerch related to therapy using vinorelbine combined with platinum-based compounds is still scarce in Indonesia. The aim of this study was to compare the efficacy and tolerability between vinorelbine and carboplatin with vinorelbin and cisplatin in stage III-IV epidermal growth factor receptor (EGFR) mutations-negative non-small cell lung cancer (NSCLC). Methods The participants were divided into two groups—group I(vinorelbine–carboplatin) and group II (vinorelbine–cisplatin). The participants were assessed based on several measurement criteria. Not only Eq-5D was performed, but the body weight and response evaluation criteria for solid tumors (RECIST) were also examined. The participants received chemotherapy for four cycles (1 cycle = 21 days). Results The quality of life was considered stable in 60% of group I and 60% of group II (p=0.255). In both groups, 46.67% of participants had an increased body weight, while the other 20.00% was stable (p = 1.000). In terms of RECIST evaluation after the second cycle, 80.00% of group I and 86.67% of group II were considered to have a stable disease, with 20% of group I and none of group II had partial response (p = 0.027). However, after the fourth cycle, there were no significant difference between the groups (p = 0.734). Conclusion In EGFR mutation-negative NSCLC patients, the combination of vinorelbine and carboplatin showed comparable outcomes to vinorelbine and cisplatin chemotherapy with no significant differences.

Challenges on the effect of cell phone radiation on mammalian embryos and fetuses: a review of the literature

Zygote ◽  
2021 ◽  
pp. 1-7
Author(s):  
Maryam Mahaldashtian ◽  
Mohammad Ali Khalili ◽  
Fatemeh Anbari ◽  
Mohammad Seify ◽  
Manuel Belli
Keyword(s):  
Embryo Development ◽  
Animal Studies ◽  
Cell Phones ◽  
Cellular Phone ◽  
The Body ◽  
Human Embryos ◽  
Success Rates ◽  
Wide Range

Summary Cell phones operate with a wide range of frequency bands and emit radiofrequency-electromagnetic radiation (RF-EMR). Concern on the possible health hazards of RF-EMR has been growing in many countries because these RF-EMR pulses may be absorbed into the body cells, directly affecting them. There are some in vitro and in vivo animal studies related to the consequences of RF-EMR exposure from cell phones on embryo development and offspring. In addition, some studies have revealed that RF-EMR from cellular phone may lead to decrease in the rates of fertilization and embryo development, as well as the risk of the developmental anomalies, other studies have reported that it does not interfere with in vitro fertilization or intracytoplasmic sperm injection success rates, or the chromosomal aberration rate. Of course, it is unethical to study the effect of waves generated from cell phones on the forming human embryos. Conversely, other mammals have many similarities to humans in terms of anatomy, physiology and genetics. Therefore, in this review we focused on the existing literature evaluating the potential effects of RF-EMR on mammalian embryonic and fetal development.

ANP kinetics in normal men: in vivo measurement by a tracer method and correlation with sodium intake

1993 ◽  
Vol 264 (3) ◽  
pp. F480-F489 ◽  
Author(s):  
G. Iervasi ◽  
A. Clerico ◽  
S. Berti ◽  
A. Pilo ◽  
F. Vitek ◽  
...  
Keyword(s):  
High Performance ◽  
Sodium Intake ◽  
Mean Transit Time ◽  
Normal Subjects ◽  
The Body ◽  
Metabolic Clearance ◽  
Healthy Human ◽  
Large Space ◽  
Wide Range

125I-labeled atrial natriuretic peptide (ANP) was bolus injected into seven healthy human male subjects on an unrestricted diet (sodium intake ranging from 80 to 300 mmol/day). A high-performance liquid chromatographic procedure was used to purify the labeled hormone and the principal labeled metabolites in venous plasma samples collected up to 50 min after injection. The main ANP kinetic parameters were derived from the disappearance curves of the 125I-ANP, which were satisfactorily fitted by a biexponential function in all subjects. Newly produced ANP initially distributes in a large space (plasma-equivalent volume is 12.1 +/- 3.6 l/m2 body surface); the hormone rapidly leaves this sampling space through both degradation and distribution in peripheral spaces, as indicated by the single-pass mean transit time through the sampling space (3.9 +/- 1.2 min). The mean residence time in the body (22.7 +/- 23.1 min) and the plasma-equivalent total distribution volume (30.9 +/- 12.0 l/m2) indicate that ANP is also widely distributed outside the initial space. Metabolic clearance rate (MCR) values were distributed across a wide range (from 740 to 2,581 ml.min-1 x m-2) and were shown to correlate strongly with the daily urinary excretion of sodium. These results indicate that: 1) newly produced ANP is rapidly distributed and degraded, 2) the body pool of the hormone can be considered as a combination of two exchanging spaces, 3) circulating ANP is < or = 1/15 of the body pool, and 4) MCR of ANP is closely related to sodium intake, at least in normal subjects on a free sodium intake diet.

scholarly journals Cleaved CD31 as a target for in vivo molecular imaging of inflammation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jonathan Vigne ◽  
Sylvie Bay ◽  
Rachida Aid-Launais ◽  
Guillaume Pariscoat ◽  
Guillaume Rucher ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Molecular Form ◽  
Positive Control ◽  
Negative Control ◽  
Stability Study ◽  
Biodistribution Studies ◽  
Wide Range ◽  
Significant Difference

AbstractThere is a need for new targets to specifically localize inflammatory foci, usable in a wide range of organs. Here, we hypothesized that the cleaved molecular form of CD31 is a suitable target for molecular imaging of inflammation. We evaluated a bioconjugate of D-P8RI, a synthetic peptide that binds all cells with cleaved CD31, in an experimental rat model of sterile acute inflammation. Male Wistar rats were injected with turpentine oil into the gastrocnemius muscle two days before 99mTc-HYNIC-D-P8RI (or its analogue with L-Proline) SPECT/CT or [18F]FDG PET/MRI. Biodistribution, stability study, histology, imaging and autoradiography of 99mTc-HYNIC-D-P8RI were further performed. Biodistribution studies revealed rapid elimination of 99mTc-HYNIC-D-P8RI through renal excretion with almost no uptake from most organs and excellent in vitro and in vivo stability were observed. SPECT/CT imaging showed a significant higher 99mTc-HYNIC-D-P8RI uptake compared with its analogue with L-Proline (negative control) and no significant difference compared with [18F]FDG (positive control). Moreover, autoradiography and histology revealed a co-localization between 99mTc-HYNIC-D-P8RI uptake and inflammatory cell infiltration. 99mTc-HYNIC-D-P8RI constitutes a new tool for the detection and localization of inflammatory sites. Our work suggests that targeting cleaved CD31 is an attractive strategy for the specific in vivo imaging of inflammatory processes.

TRIAP1 Inhibition Activates the Cytochrome c/Apaf-1/Caspase-9 Signaling Pathway to Enhance Human Ovarian Cancer Sensitivity to Cisplatin

Chemotherapy ◽  
2019 ◽  
Vol 64 (3) ◽  
pp. 119-128 ◽  
Author(s):  
Tian-Mei Zhang
Keyword(s):  
Ovarian Cancer ◽  
Nude Mice ◽  
Cell Apoptosis ◽  
Caspase 9 ◽  
Ovarian Carcinoma Cell Line ◽  
Skov3 Cells ◽  
Cyt C ◽  
Sirna Group

Objective: To investigate whether TRIAP1inhibition affects the ovarian cancer cell resistance to cisplatin (DDP) via the Cyt c/Apaf-1/caspase-9 pathway by in vitro and in vivo experiments. Methods: CCK8 assay was performed to find out how treatment with both TRIAP1 siRNA and DDP affects the cell viability of SKOV3 cells and DDP-resistant human ovarian carcinoma cell line SKOV3/DDP. SKOV3/DDP cells were transfected with control siRNA or TRIAP1 siRNA before 24 h of treatment with DDP (5 μg/mL). Flow cytometry was employed to detect cell apoptosis and Western blot to examine the expressions of Cyt c/Apaf-1/caspase-9 pathway-related proteins. SKOV3/DDP cells transfected with control siRNA or TRIAP1 siRNA were subcutaneously injected into BALB/c-nu/nu nude mice followed by the intraperitoneal injection of DDP (4 mg/kg). Cyt c/Apaf-1/caspase-9 pathway in transplanted tumors was detected by immunohistochemistry. Results: TRIAP1 expression declined in SKOV3 cells when compared with SKOV3/DDP cells. The proliferation rate was lower in SKOV3/DDP cells transfected with TRIAP1 siRNA combined with treatment of DDP (1, 2, 4, 6, 8, 16, 32 μg/mL) than in those transfected with control siRNA. Moreover, the TRIAP1 siRNA group had an increased SKOV3/DDP cell apoptosis rate with the activation of the Cyt c/Apaf-1/caspase-9 pathway. During DDP treatment, nude mice in TRIAP1 siRNA group had slower growth and smaller size of transplanted tumor than those in control siRNA group, with increased expression of Cyt c, Apaf-1, and caspase-9. Conclusion: TRIAP1 inhibition may enhance the sensitivity of SKOV3/DDP cells to cisplatin via activation of the Cyt c/Apaf-1/caspase-9 pathway.

scholarly journals High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution

Blood ◽  
2002 ◽  
Vol 99 (12) ◽  
pp. 4357-4363 ◽  
Author(s):  
Suparno Chakrabarti ◽  
Stephen Mackinnon ◽  
Raj Chopra ◽  
Panagiotis D. Kottaridis ◽  
Karl Peggs ◽  
...  
Keyword(s):  
Immune Reconstitution ◽  
De Novo ◽  
Unrelated Donor ◽  
Cmv Infection ◽  
Nonmyeloablative Stem Cell Transplantation ◽  
Wide Range ◽  
Significant Difference ◽  
High Incidence ◽  
Cmv Disease

Nonmyeloablative conditioning is increasingly used for transplantation in a wide range of diseases, but little is known about its impact on the incidence of infections and immune reconstitution. We examined the pattern and outcome of cytomegalovirus (CMV) infections monitored by polymerase chain reaction–based assays and treated preemptively in 101 patients following nonmyeloablative conditioning containing in vivo Campath-1H. Fifty-one patients (50%) had a CMV infection at a median of 27 days after transplantation with a probability of 84.8% in patients at risk of CMV infection. The probability of recurrence of CMV infection before and after 100 days was 53.6% and 46.6%, respectively, and was more common in unrelated donor transplant recipients. All 3 patients who developed CMV disease died of this complication. The 2 patients with late CMV disease had grade III to IV graft-versus-host-disease (GVHD), which occurred de novo in only 4% of patients and in another 10% following donor lymphocyte infusions. The median time to CD4+ T-cell count more than 200/μL was 9 months in the 48 patients studied. The probabilities of overall survival and nonrelapse mortality at 18 months were 65% and 27.8%, respectively, with no significant difference in survival between CMV-infected and -uninfected patients. The use of Campath-1H appeared to be associated with a low incidence of GVHD but a high incidence of CMV infections and prolonged immune paresis.

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