Evaluation of the Therapeutic Effect of Magneto-Nanomicelles Based on Magneto-Thermal and Photo-Thermal Therapy

2020 ◽  
Vol 20 (12) ◽  
pp. 7406-7411
Author(s):  
Weiwen Lin ◽  
Zhizhong Chen ◽  
Jiaoning Fang ◽  
Jingming Chen ◽  
Jiangao Xie ◽  
...  

In this study, we investigated the hyperthermia efficiency of magnetic hyperthermia therapy (MHT), photo-thermal therapy (PTT), and the combination of both techniques by employing SPIO-based magneto-nanomicelles as the heating agents. Magneto-nanomicelles in aqueous suspension were exposed to 808-nm laser irradiation (PTT mode), alternating magnetic field (MHT mode), and both modalities (DUAL mode). All the three methods can offer effective temperature increases (above 20 °C). DUAL-mode resulted in an approximately 2-fold increase in heating efficiency (36 °C) compared with PTT or MHT alone. For in vivo experiments, a total of 24 Lewis carcinoma-bearing mice were randomly divided into four groups: the control group (no therapy), PTT, MHT, and DUAL group. In the three therapy groups, magneto-nanomicelles were injected into the tumor and the corresponding treatment measures were performed every other day for a total of three times each. MRI scans were used to calculate tumor volume after each treatment. One-way analysis of variance (ANOVA) was employed to compare the curative effect of different treatment groups. Compared with the control group, PTT, MHT, and DUAL groups all showed a significant inhibitory effect on tumor volume (P < 0.05). In the DUAL group, the mean tumor volume was smaller than that of the PTT or the MHT group. Our work demonstrated that hyperthermia using SPIO-based magnetonanomicelles has a remarkable suppressive effect in anticancer therapy. Moreover, the combined model of hyperthermia in vivo can achieve synthetic effects with shorter healing time by using the same magneto-nanomicelles.

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi72-vi73
Author(s):  
Xiang-rong Ni ◽  
Jing Wang ◽  
Fu-rong Chen ◽  
Hai-ping Cai ◽  
Yan-jiao Yu ◽  
...  

Abstract OBJECTIVE Temozolomide (TMZ), is the first line chemotherapeutic drug for glioma. Previous studies have suggested that interferon (IFN) and levetiracetam (LEV) could respectively reverse the resistance of TMZ by down-regulating MGMT expression. This study, we aim to investigate the therapeutic effect of a cocktail chemotherapy regimen combining TMZ, LEV, IFN in vivo. METHODS Glioma cell lines U251 and SKMG-4 (MGMT protein expression positive), U138 and GSC-1(MGMT protein expression negative) were used for producing xenograft tumors. The xenograft tumors were established by subcutaneously injecting 1×106 glioma cells into female BALB/C nude mice and divided into 5 treatment groups: Control, TMZ, TMZ+IFN, TMZ+LEV, TMZ+LEV+IFN. The treatment with TMZ (50 mg/kg, i.p.), IFN (2×105 IU, s.c.), LEV (150 mg/kg, i.p.) once a day for five consecutive days and xenograft tumors were measured every two days. RESULTS We identified that U138, U251, SKMG-4 tumor growth among TMZ, TMZ+IFN, TMZ+LEV, TMZ+LEV+IFN were all significantly inhibited (P< 0.05), compared with the control. As for U251 and SKMG-4, tumor killing effect of all 4 treatment groups were not different (P > 0.05). In the treatment of mice bearing U138 glioma, the tumor weight of TMZ+LEV+IFN (0.2688±0.1169 g) group was the lowest and significantly lower than that of TMZ+LEV (0.6574±0.08174g, P=0.0261), TMZ+IFN(0.6108±0.07317 g, P=0.0381), and TMZ (0.9054±0.07154 g, P=0.0017) group. Glioma stem cells GSC-1 was highly resistant to TMZ, tumor volume of TMZ group was not different from control group (P >0.05). While compared with TMZ (1.993±0.1274 g) group, in TMZ+IFN (1.506±0.1223g, P=0.0203), TMZ+LEV (1.178±0.1807g, P=0.0042), and TMZ+LEV+IFN (1.049±0.2171 g, P=0.0038) groups, GSC-1 tumor growth were significantly inhibited(P< 0.05). CONCLUSION Our data demonstrate that both IFN and LEV can sensitize TMZ effect on glioma in vivo, even for MGMT(+) tumors, and TMZ-LEV-IFN cocktail regimen seems the best. Key words: glioma, TMZ, LEV, IFN


Author(s):  
Subeer Roy ◽  
Diksha Kumari ◽  
Mainak Chakraborty ◽  
Pallab Kanti Haldar

Objective: Methanol extract of Calamus rotang (MECR) root was appraised as a spotlight for the candidate of anticancer activity through the vehicle (Ehrlich Ascites Carcinoma) on Swiss albino mice.Methods: In vitro cytotoxicity assay has been accessed by trypan blue and MTT assay. In vivo anticancer activity was done using EAC cells (2 × 106) where in each groups mice were 6. After treatment with MECR at the lower dose of 200 and higher dose of 400 mg/kg respectively for 9 d, half of the mice of each group were sacrificed and the rest were kept to check prolongation of life span. The anticancer potential of MECR was evaluated by tumor volume, viable and nonviable tumor cell count, tumor weight, hematological parameters, biochemical estimations and Furthermore, tissue antioxidant parameters. Besides, solid tumor activity was also inspected.Results: In MECR treated groups (200 and 400 mg/kg) tumor volume, packed cell volume and viable cell count was significantly lessened as compared to that of the EAC control group. Life span, most reliable criteria for anticancer study, increased quite surprisingly by 50% and 100% in a dose dependant manner while compared to EAC control group. The hematological, biochemical and liver tissue antioxidant parameter are significantly (p<0.05) restored along with solid tumor case study (solid tumor volume) towards the normal level after treatment with MECR.Conclusion: From the above study it can be inferred that the MECR has impressive anticancer activity in dose dependent way.


Antibodies ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 51
Author(s):  
Ellinor I. Peerschke ◽  
Elisa de Stanchina ◽  
Qing Chang ◽  
Katia Manova-Todorova ◽  
Afsar Barlas ◽  
...  

gC1qR is highly expressed in breast cancer and plays a role in cancer cell proliferation. This study explored therapy with gC1qR monoclonal antibody 60.11, directed against the C1q binding domain of gC1qR, in a murine orthotopic xenotransplant model of triple negative breast cancer. MDA231 breast cancer cells were injected into the mammary fat pad of athymic nu/nu female mice. Mice were segregated into three groups (n = 5, each) and treated with the vehicle (group 1) or gC1qR antibody 60.11 (100 mg/kg) twice weekly, starting at day 3 post-implantation (group 2) or when the tumor volume reached 100 mm3 (group 3). At study termination (d = 35), the average tumor volume in the control group measured 895 ± 143 mm3, compared to 401 ± 48 mm3 and 701 ± 100 mm3 in groups 2 and 3, respectively (p < 0.05). Immunohistochemical staining of excised tumors revealed increased apoptosis (caspase 3 and TUNEL staining) in 60.11-treated mice compared to controls, and decreased angiogenesis (CD31 staining). Slightly decreased white blood cell counts were noted in 60.11-treated mice. Otherwise, no overt toxicities were observed. These data are the first to demonstrate an in vivo anti-tumor effect of 60.11 therapy in a mouse model of triple negative breast cancer.


2011 ◽  
Vol 365 ◽  
pp. 222-227
Author(s):  
Li Tang ◽  
Li Yu

Recent studies have shown that Genistein can obviously suppress growth of gynecologic carcinoma. In this study we examined whether Genistein and Cisplatin, alone and in combination, exhibited a inhibitory effect on the growth of ovarian carcinoma. SKOV3 cells were treated with 20µM Genistein, 20µM Cisplatin and combination group (G+C) for 24 to 72 hours, antiproliferative effect was tested by MTT method. Apoptosis was evaluated using flow cytometry and transmission electron microscopy. Then the transplanted xenografts were treated with Genistein and Cisplatin, the tumor volume and tumor weight were measured, HE staining were performed for morphologic observation. A time and dose-dependent growth inhibition was observed. When treated the cells with 20µM Genistein, 20µMCisplatin and combination group (G+C), compared with the control group, the growth of cells in different treatment group was inhibited, while the combination of Genistein and Cisplatin showed significant inhibition effect than single agent. When Genistein (0.4mg/kg, s.c.) treated the transplanted xenograft in vivo, the tumor volume and tumor weight decreased, T/C ratio (mean volume of treated group/mean volume of control group) also was reduced compared to untreated group, and extensive necrotic areas in the tumor treated with Genistein and Cisplatin appeared in HE section. A weight loss of nude mice after treatment with Genistein was not significant as compared with the control group. And when treated with Genistein (0.4mg/kg, s.c.) and Cisplatin (4mg/kg, i.v.), it showed a synergistic effect. Genistein and Cisplatin, alone and in combination, suppress cell growth. The combination of Genistein and Cisplatin, as compared to single treated group, caused a synergistic increase in antiproliferative effect on SKOV3 cells. The implication for treatment of ovarian cancer may be combination of Genistein and Cisplatin. Further studies are needed to supply more evidence.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hye Rim Cho ◽  
Nisha Kumari ◽  
Nishant Thakur ◽  
Hien Thi Vu ◽  
Hyeonjin Kim ◽  
...  

Abstract Glioblastoma multiforme (GBM) is one of the most aggressive human tumors with poor survival rates. The current standard treatment includes chemotherapy with temozolomide (TMZ), but acquisition of resistance is a persistent clinical problem limiting the successful treatment of GBM. The purpose of our study was to investigate therapeutic effects of nitroxoline (NTX) against TMZ-resistant GBM in vitro and in vivo in TMZ-resistant GBM-bearing mouse model, which was correlated with diffusion-weighted imaging (DWI). For in vitro study, we used TMZ-resistant GBM cell lines and evaluated therapeutic effects of NTX by clonogenic and migration assays. Quantitative RT-PCR was used to investigate the expression level of TMZ-resistant genes after NTX treatment. For in vivo study, we performed 9.4 T MR imaging to obtain T2WI for tumor volume measurement and DWI for assessment of apparent diffusion coefficient (ADC) changes by NTX in TMZ-resistant GBM mice (n = 8). Moreover, we performed regression analysis for the relationship between ADC and histological findings, which reflects the changes in cellularity and apurinic/apyrimidinic endonuclease-1 (APE-1) expression. We observed the recovery of TMZ-induced morphological changes, a reduced number of colonies and a decreased rate of migration capacity in TMZ-resistant cells after NTX treatment. The expression of APE-1 was significantly decreased in TMZ-resistant cells after NTX treatment compared with those without treatment. In an in vivo study, NTX reduced tumor growth in TMZ-resistant GBM mice (P = 0.0122). Moreover, ADC was increased in the NTX-treated TMZ-resistant GBM mice compared to the control group (P = 0.0079), which was prior to a tumor volume decrease. The cellularity and APE-1 expression by histology were negatively correlated with the ADC value, which in turn resulted in longer survival in NTX group. The decreased expression of APE-1 by NTX leads to therapeutic effects and is inversely correlated with ADC in TMZ-resistant GBM. Therefore, NTX is suggested as potential therapeutic candidate against TMZ-resistant GBM.


2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 271-271
Author(s):  
Amr Ammar ◽  
Mohamed Hessein ◽  
Emma Guns ◽  
Mei Chin ◽  
Abul Bashar Helaluddin ◽  
...  

271 Background: Ancient traditional physicians from many countries used leeching to treat a wide range of diseases for thousands of years. A large number of peptides and proteins have been identified and characterized in leech saliva extract (LSE), including anti-thrombotic agents, cancer metastasis inhibitors and anti-microbials Currently, leech therapy is established as an important tool in microsurgery and reconstructive operations having demonstrated superior clinical outcomes for the optimal salvage of grafted tissues. Methods: In the current study, we have determined the in vivo efficacy of LSE from (Huridinaria manillensis) on castration resistant LNCaP xenograft mouse model. Mice were divided into three groups of six, mice were subcutaneously injected with either LSE (5 mg/kg), docetaxel (10 mg/kg), or vehicle once a week. PSA and tumor volume were measured weekly. After four weeks of treatment, mice were euthanized, tumors and organs were collected for transcriptome and immunohistochemical (IHC) analysis. Results: There was a significant decrease in the tumor volume and PSA with either docetaxel (10mg/kg) or LSE (5 mg/kg) treated groups compared to the control. While there was no significant difference between the anti-tumor activity of docetaxel (10mg/kg) and LSE (5 mg/kg). IHC showed significant increase in caspase-3 and significant decrease in Ki-67 and PCNA expression in the LSE treated mice compared to the control group. Interestingly, transcriptome analysis of tumor samples showed that LSE modulated cytokine production, monocyte adhesion, steroidogenesis, and P38 MAPK signaling pathways. Conclusions: LSE has significant anti-tumor activity in LNCaP tumor xenograft models with no apparent side effects. This can be attributed, at least partly, to its inhibition of cellular proliferation, induction of apoptosis, modulation of immunity and steroidogenesis.


2020 ◽  
Vol 245 (15) ◽  
pp. 1385-1394
Author(s):  
Jing Wang ◽  
Yanmin Dong ◽  
Qiuming Li

Retinoblastoma is common primary intraocular malignancy of infants and childhood. Neferine is a major bisbenzylisoquinoline alkaloid derived from the lotus plumule in Nelumbo nucifera. This study evaluated the mitigation role of Neferine on retinoblastoma in vitro and in vivo. Xenotransplantation model was established by injecting WERI-Rb-1 cells subcutaneously. Upon induction of retinoblastoma , mice were intraperitoneally injected with Neferine (0, 0.5, 1, 2 mg/kg) or ethanol every 3 days for 30 days. Tumor weight and tumor volume were measured every three days and compared between four groups. Then, mice were sacrificed and immunohistochemical examination was performed to compare Ki67, VEGF content between groups. WERI-Rb-1 cells were used for in vitro experiments and the anti-angiogenic role of Neferine was assessed by analyzing nodes/HPF number. In WERI-Rb-1 xenotransplantation model, compared with control group, 1 mg/kg Neferine treatment significantly inhibited tumor weight (0.39 ± 0.04 g vs. 0.25 ± 0.03 g, P< 0.05) and tumor volume (2163 ± 165 mm3 vs. 1276 ± 108 mm3, P< 0.05) after 30 days. Compared with ethanol-injected mice, 2 μM Neferine treatment significantly enhanced apoptosis rate (2.1 ± 0.6% vs. 14.6 ± 2.6%, P< 0.05), accompany downregulation of Ki67 (0.09 ± 0.02% vs. 0.01 ± 0.004%, P< 0.05) and VEGF (0.28 ± 0.04% vs. 0.05 ± 0.03%, P< 0.05) expression. Additionally, 2 μM Neferine treatment significantly decreased JC-1 red/green percentage. High-dose Neferine could decrease retinoblastoma angiogenesis in association with a significant inhibition on tumor growth and invasion. These findings suggested that Neferine could be a new treatment or adjuvant against retinoblastoma.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ali Ashkbar ◽  
Fatemeh Rezaei ◽  
Farnoosh Attari ◽  
Saboura Ashkevarian

AbstractBreast cancer is a neoplastic disease with a high mortality rate among women. Recently, photodynamic therapy (PDT) and photothermal therapy (PTT) attracted considerable attention because of their minimal invasiveness. The PTT approach works based on hyperthermia generation, and PDT approach employs laser irradiation to activate a reagent named photosensitizer. Therefore, in the current paper, a dual-functioned nanocomposite (NC) was designed for the treatment of breast cancer model in Balb/c mice with the combination of photodynamic and photothermal approaches. Transmission electron microscopy, UV–visible spectroscopy, FTIR, and XRD were employed to validate the nanostructure and silica coating and curcumin (CUR) immobilization on the Fe3O4 nanoparticles. The effect of Fe3O4/SiO2-CUR combined with PDT and PTT was assessed in vivo on the breast tumor mice model, and immunohistochemistry (IHC) was employed to evaluate the expression of apoptotic Bax and Caspase3 proteins. The TEM images, UV–visible absorption, and FTIR spectra demonstrated the successful immobilization of curcumin molecules on the surface of Fe3O4/SiO2. Also, MTT assay confirmed the nontoxic nature of Fe3O4/SiO2 nanoparticles in vitro. In the breast tumor mice model, we have assessed six treatment groups, including control, CUR + PDT, Blue + NIR (near-infrared) lasers, NC, NC + PTT, and NC + PDT + PTT. The tumor volume in the NC + PDT + PTT group showed a significant reduction compared to other groups (p < 0.05). More interestingly, the tumor volume of NC + PDT + PTT group showed a 27% decrease compared to its initial amount. It should be noted that no detectable weight loss or adverse effects on the vital organs was observed due to the treatments. Additionally, the IHC data represented that the expression of proapoptotic Bax and Caspase3 proteins were significantly higher in the NC + PDT + PTT group compared to the control group, indicative of apoptosis. To conclude, our data supported the fact that the NC + PDT + PTT strategy might hold a promising substitute for chemotherapy for the treatment of triple-negative breast cancers.


Author(s):  
Arthur J. Wasserman ◽  
Azam Rizvi ◽  
George Zazanis ◽  
Frederick H. Silver

In cases of peripheral nerve damage the gap between proximal and distal stumps can be closed by suturing the ends together, using a nerve graft, or by nerve tubulization. Suturing allows regeneration but does not prevent formation of painful neuromas which adhere to adjacent tissues. Autografts are not reported to be as good as tubulization and require a second surgical site with additional risks and complications. Tubulization involves implanting a nerve guide tube that will provide a stable environment for axon proliferation while simultaneously preventing formation of fibrous scar tissue. Supplementing tubes with a collagen gel or collagen plus extracellular matrix factors is reported to increase axon proliferation when compared to controls. But there is no information regarding the use of collagen fibers to guide nerve cell migration through a tube. This communication reports ultrastructural observations on rat sciatic nerve regeneration through a silicone nerve stent containing crosslinked collagen fibers.Collagen fibers were prepared as described previously. The fibers were threaded through a silicone tube to form a central plug. One cm segments of sciatic nerve were excised from Sprague Dawley rats. A control group of rats received a silicone tube implant without collagen while an experimental group received the silicone tube containing a collagen fiber plug. At 4 and 6 weeks postoperatively, the implants were removed and fixed in 2.5% glutaraldehyde buffered by 0.1 M cacodylate containing 1.5 mM CaCl2 and balanced by 0.1 M sucrose. The explants were post-fixed in 1% OSO4, block stained in 1% uranyl acetate, dehydrated and embedded in Epon. Axons were counted on montages prepared at a total magnification of 1700x. Montages were viewed through a dissecting microscope. Thin sections were sampled from the proximal, middle and distal regions of regenerating sciatic plugs.


1990 ◽  
Vol 29 (03) ◽  
pp. 120-124
Author(s):  
R. P. Baum ◽  
E. Rohrbach ◽  
G. Hör ◽  
B. Kornhuber ◽  
E. Busse

The effect of triiodothyronine (T3) on the differentiation of cultured neuroblastoma (NB) cells was studied after 9 days of treatment with a dose of 10-4 M/106 cells per day. Using phase contrast microscopy, 30-50% of NB cells showed formation of neurites as a morphological sign of cellular differentiation. The initial rise of the mitosis rate was followed by a plateau. Changes in cyclic nucleotide content, in the triphosphates and in the activity of the enzyme ornithine decarboxylase (ODC) were assessed in 2 human and 2 murine cell lines to serve as biochemical parameters of the cell differentiation induced by T3. Whereas the cAMP level increased significantly (3 to 7 fold compared with its initial value), the cGMP value dropped to 30 to 50% of that of the control group. ATP and GTP increased about 200%, the ODC showed a decrease of about 50%. The present studies show a biphasic effect of T3 on neuroblastoma cells: the initial rise of mitotic activity is followed by increased cell differentiation starting from day 4 of the treatment.


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