Control of Ehrlich Tumor Growth by Electromagnetic Waves at Resonance Frequency (In Vivo Studies)

The paper presents the results of the research on the antitumor activity of a new drug - atomic clusters of silver (ACS), the colloidal solution of nanostructured silver bisilicate Ag6Si2O7 with particles size of 1-2 nm in deionized water. In vitro studies to evaluate the effect of various ACS concentrations in human tumor cells cultures (breast cancer, colon carcinoma and prostate cancer) were conducted. The highest antitumor activity of ACS was observed in dilutions from 2.7 mg/l to 5.1 mg/l, resulting in the death of tumor cells in all studied cell cultures. In vivo experiments on transplanted Ehrlich carcinoma model in mice consuming 0.75 mg/kg ACS with drinking water revealed significant inhibition of tumor growth since the 14th day of experiment (maximally by 52% on the 28th day, p < 0.05) in comparison with control. Subcutaneous injections of 2.5 mg/kg ACS inhibited Ehrlich's tumor growth on the 7th and 10th days of the experiment (p < 0.05) as compared to control.

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Regulation of Parathyroid Hormone-Related Peptide by Estradiol: Effect on Tumor Growth and Metastasis in Vitro and in Vivo

Endocrinology ◽

10.1210/en.2005-0062 ◽

2005 ◽

Vol 146 (7) ◽

pp. 2885-2894 ◽

Cited By ~ 22

Author(s):

S. A. Rabbani ◽

P. Khalili ◽

A. Arakelian ◽

H. Pizzi ◽

G. Chen ◽

...

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Tumor Growth ◽

Tumor Volume ◽

In Vivo Studies ◽

Promoting Effect ◽

X Ray ◽

Tumor Bearing ◽

Tumor Growth And Metastasis

Abstract We evaluated the capacity of estradiol (E2) to regulate PTHrP production, cell growth, tumor growth, and metastasis to the skeleton in breast cancer. In estrogen receptor (ER)-negative human breast cancer cells, MDA-MB-231, and cells transfected with full-length cDNA encoding ER (S-30), E2 caused a marked decrease in cell growth and PTHrP production, effects that were abrogated by anti-E2 tamoxifen. E2 also inhibited PTHrP promoter activity in S-30 cells. For in vivo studies, MDA-MB-231 and S-30 cells were inoculated into the mammary fat pad of female BALB/c nu.nu mice. Animals receiving S-30 cells developed tumors of significantly smaller volume compared with MDA-MB-231 tumor-bearing animals. This change in tumor volume was reversed when S-30 cells were inoculated into ovariectomized (OVX) hosts. Inoculation of MDA-MB-231 cells into the left ventricle resulted in the development of lesions in femora and tibia as determined by x-ray analysis. In contrast, these lesions were significantly smaller in volume and number in animals inoculated with S-30, and this lower incidence was reversed in OVX animals. Bone histological analysis showed that the tumor volume to tissue volume ratio was comparable with that seen by x-ray. Immunohistochemical analysis showed that PTHrP production was inhibited in S-30 group and restored to levels comparable to that seen in MDA-MB-231 tumor-bearing animals when S-30 cells were inoculated in OVX animals. Collectively these studies show that E2 production is inversely correlated with PTHrP production and that the growth-promoting effect of PTHrP has a direct impact on tumor growth at both nonskeletal and skeletal sites.

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Effect of cabazitaxel on the growth of human castration-refractory prostate cancer cells in vitro compared to docetaxel and on the anti-tumor properties of the angio-inhibitor PEDF in vivo.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.205 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 205-205

Author(s):

Thomas Nelius ◽

Courtney Jarvis ◽

Dalia Martinez-Marin ◽

Stephanie Filleur

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

Tumor Growth ◽

Tumor Cells ◽

Cell Lines ◽

In Vitro Cytotoxicity ◽

In Vivo Studies ◽

Raw264.7 Macrophages

205 Background: Docetaxel/DTX and cabazitaxel/CBZ have shown promise in the treatment of metastatic Castration-Refractory Prostate Cancer/mCPRC however, comparative studies are missing. Toxicities of these drugs are significant, urging the need to modify taxane regimens. Recently, low-dose metronomic/LDM treatments using conventional chemotherapeutic drugs have shown benefits in CPRC in improving the effect of anti-angiogenic agents. Previously, we have demonstrated that LDM-DTX in combination with PEDF curbs significantly CRPC growth, limits metastases formation and prolongs survival in vivo. In this study, we intended to compare the cytotoxic effect of CBZ and DTX on CRPC cells in vitro and CL1 tumors in vivo. Methods: PC3, DU145 cell lines were from ATCC.CL1 cells were obtained from androgen-deprived LNCaP cells. Cell proliferation was assessed by crystal violet staining and cell cycle analyses. In vitro cytotoxicity assays were performed on CL1 cells/RAW264.7 macrophages co-cultures treated with PEDF and increasing doses of taxanes. For the in vivo studies, CL1 cells were engineered to stably express the DsRed Express protein +/- PEDF. PEDF anti-tumor effects were assessed on s.c. xenografts treated with DTX (5mg/kg ip ev. 4 day) as reference, CBZ (5mg/kg ip ev. 4 days, 1mg/kg for 10 days, 0.5mg/kg q.a.d. and 0.1mg/kg daily) or placebo. Results: CBZ limits cell proliferation with a greater efficacy than DTX in all CRPC cell lines tested. DU145 presented the largest difference. High doses of taxane blocked tumor cells in mitosis, whereas LDM increased the SubG1 population. This effect was significantly higher in DU145 cells treated with CBZ. In vivo, 5mg/kg CBZ delayed tumor growth more efficiently than 5mg/kg DTX. PEDF/5mg/kg CBZ markedly delayed tumor growth compared to all treatments. Finally, engulfment of tumor cells by macrophages was higher in combined treatments suggesting an inflammation-related process. Conclusions: CBZ is more efficient than DTX both in vitro and in vivo.The data also reinforce PEDF as a promising anti-neoplasic agent in combination with LDM taxane chemotherapies.

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Cytotoxic effect of Montivipera bornmuelleri’s venom on cancer cell lines: in vitro and in vivo studies

PeerJ ◽

10.7717/peerj.9909 ◽

2020 ◽

Vol 8 ◽

pp. e9909

Author(s):

Carol Haddoub ◽

Mohamad Rima ◽

Sandrine Heurtebise ◽

Myriam Lawand ◽

Dania Jundi ◽

...

Keyword(s):

Tumor Growth ◽

Cell Lines ◽

Cytotoxic Effect ◽

In Vivo Studies ◽

Dependent Manner ◽

In Vivo Testing ◽

Murine Fibrosarcoma ◽

Dose Dependent

Background Montivipera bornmuelleri’s venom has shown immunomodulation of cytokines release in mice and selective cytotoxicity on cancer cells in a dose-dependent manner, highlighting an anticancer potential. Here, we extend these findings by elucidating the sensitivity of murine B16 skin melanoma and 3-MCA-induced murine fibrosarcoma cell lines to M. bornmuelleri’s venom and its effect on tumor growth in vivo. Methods The toxicity of the venom on B16 and MCA cells was assessed using flow cytometry and xCELLigence assays. For in vivo testing, tumor growth was followed in mice after intratumoral venom injection. Results The venom toxicity showed a dose-dependent cell death on both B16 and MCA cells. Interestingly, overexpression of ovalbumin increased the sensitivity of the cells to the venom. However, the venom was not able to eradicate induced-tumor growth when injected at 100 µg/kg. Our study demonstrates a cytotoxic effect of M. bornmuelleri’s venom in vitro which, however, does not translate to an anticancer action in vivo.

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Targeting OLFML3 in Colorectal Cancer Suppresses Tumor Growth and Angiogenesis, and Increases the Efficacy of Anti-PD1 Based Immunotherapy

Cancers ◽

10.3390/cancers13184625 ◽

2021 ◽

Vol 13 (18) ◽

pp. 4625

Author(s):

Jimmy Stalin ◽

Beat A. Imhof ◽

Oriana Coquoz ◽

Rachel Jeitziner ◽

Philippe Hammel ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Growth ◽

Molecular Subtype ◽

Human Cancer ◽

Tumor Development ◽

Tumor Grade ◽

Tissue Expression ◽

In Vivo Studies

The role of the proangiogenic factor olfactomedin-like 3 (OLFML3) in cancer is unclear. To characterize OLFML3 expression in human cancer and its role during tumor development, we undertook tissue expression studies, gene expression analyses of patient tumor samples, in vivo studies in mouse cancer models, and in vitro coculture experiments. OLFML3 was expressed at high levels, mainly in blood vessels, in multiple human cancers. We focused on colorectal cancer (CRC), as elevated expression of OLFML3 mRNA correlated with shorter relapse-free survival, higher tumor grade, and angiogenic microsatellite stable consensus molecular subtype 4 (CMS4). Treatment of multiple in vivo tumor models with OLFML3-blocking antibodies and deletion of the Olfml3 gene from mice decreased lymphangiogenesis, pericyte coverage, and tumor growth. Antibody-mediated blockade of OLFML3 and deletion of host Olfml3 decreased the recruitment of tumor-promoting tumor-associated macrophages and increased infiltration of the tumor microenvironment by NKT cells. Importantly, targeting OLFML3 increased the antitumor efficacy of anti-PD-1 checkpoint inhibitor therapy. Taken together, the results demonstrate that OLFML3 is a promising candidate therapeutic target for CRC.

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Evaluation of the Anti-Tumor Activity of Niclosamide Nanoliposomes Against Colon Carcinoma

Current Molecular Pharmacology ◽

10.2174/1874467212666190821142721 ◽

2020 ◽

Vol 13 (3) ◽

pp. 245-250

Author(s):

Mahdi Hatamipour ◽

Mahmoud R. Jaafari ◽

Amir A. Momtazi-Borojeni ◽

Mahin Ramezani ◽

Amirhossein Sahebkar

Keyword(s):

Tumor Growth ◽

Experimental Model ◽

Colon Carcinoma ◽

Carcinoma Cells ◽

In Vivo Studies ◽

Colon Carcinoma Cells ◽

Ct26 Colon Carcinoma ◽

Anti Tumor Activity

Background and Aims: Niclosamide is an established anti-helminthic drug, which has recently been shown to inhibit the growth of various cancer cells. To exploit the potential anti-tumor activity of this drug for systemic use, the problem of low aqueous solubility should be addressed. The present study tested the in vivo anti-tumor effects of a recently developed nanoliposomal preparation of niclosamide in an experimental model of colon carcinoma. Methods : The cytotoxicity of nanoliposomal niclosamide on CT26 colon carcinoma cells was evaluated using the MTT test. Inhibition of tumor growth was investigated in BALB/c mice bearing CT26 colon carcinoma cells. The animals were randomly divided into 4 groups including: 1) untreated control, 2) liposomal doxorubicin (15 mg/kg; single intravenous dose), 3) liposomal niclosamide (1 mg/kg/twice a week; intravenously for 4 weeks), and 4) free niclosamide (1 mg/kg/twice a week; intravenously for 4 weeks). To study therapeutic efficacy, tumor size and survival were monitored in 2-day intervals for 40 days. Results: In vitro results indicated that nanoliposomal and free niclosamide could exert cytotoxic effects with IC50 values of 4.5 and 2.5 μM, respectively. According to in vivo studies, nanoliposomal niclosamide showed a higher growth inhibitory activity against CT26 colon carcinoma cells compared with free niclosamide as revealed by delayed tumor growth and prolongation of survival. Conclusion : Nnaoliposomal encapsulation enhanced anti-tumor properties of niclosamide in an experimental model of colon carcinoma.

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Studies of pemetrexed and gemcitabine, alone and in combinations, in human lung cancer models

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.17114 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 17114-17114 ◽

Cited By ~ 2

Author(s):

D. C. Chan ◽

V. J. Chen ◽

Z. Zhang ◽

B. Helfrich ◽

F. R. Hirsch ◽

...

Keyword(s):

Tumor Growth ◽

Cell Lines ◽

In Vivo Studies ◽

Human Lung Cancer ◽

Dependent Manner ◽

Antitumor Effects ◽

Nude Rats ◽

Combination Regimens

17114 Background: Gemcitabine (GEM) is a deoxycytidine analog that inhibits DNA synthesis. Pemetrexed (ALIMTA, PEM) is a novel antifolate inhibiting multiple enzymes targets, including thymidylate synthase (TS). This study aimed at evaluating the antitumor effects of these antimetabolites against NSCLC and SCLC tumor models. Methods: In vitro growth inhibition (IC50) studies were done by 6-days MTT assays against a panel of 20 NSCLC and 17 SCLC cell lines. In vivo studies used only NSCLC H2122 tumor line, implanted either subcutaneously in athymic nude mice or orthotopically in athymic nude rats. Drugs were given via the ip route at the designated schedules. Results: Against NSCLC and SCLC cell lines, the averaged IC50s of GEM were 0.015 ± 0.008 μM and 0.055 ± 0.04 μM respectively. The corresponding averaged IC50s for PEM were 0.65 ± 0.2 μM and 0.091±0.018 μM respectively. When H2122 tumors reached 50–100mg, mice were treated with 10 daily doses of PEM at 100, 200 and 300 mg/kg, or three doses of GEM every 4 days at 30, 60 and 120 mg/kg. PEM delayed tumor growth by 12 to 18 days, and GEM delayed by 10 to 14 days, relative to vehicle control. Results of three combination regimens with GEM (30 mg/kg) and PEM (100 mg/kg) were: (1) GEM → PEM gave intermediate activities between the two single agents, but was toxic to animals; (2) PEM and GEM given concurrently were more active than single agents alone and delayed tumor growth by 12 days with some toxic side effects; (3) PEM → GEM was better than the single agents alone, and delayed tumor growth by ∼14 days without toxicity. Athymic nude rats bearing orthotopic H2122 tumors given PEM daily at 50, 100 and 200 mg/kg for 21 days had significantly prolonged survival, but not in a dose-dependent manner. PEM at 50 mg/kg was more effective than doses at 100 or 200 mg/kg. GEM was toxic to nude rats due to poor plasma deamination of GEM. Conclusions: In vitro, PEM was more potent against SCLC than NSCLC cell lines, but GEM had similar activities against all lung lines tested. Studies of H2122 xenografts in rodent supported PEM → GEM as the preferred sequence for the combined administration of these two drugs. [Table: see text]

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Inhibition of Src and insulin/insulin-like growth factor-1 receptor (IR/IGF-1R) on tumors and bone turnover in prostate cancer (PCa) models in vivo compared with inhibition of either kinase alone.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.61 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 61-61

Author(s):

Farshid Dayyani ◽

Nila Parikh ◽

Jian H. Song ◽

John C. Araujo ◽

Joan M. Carboni ◽

...

Keyword(s):

Bone Turnover ◽

Tumor Growth ◽

Bone Turnover Markers ◽

Bone Destruction ◽

In Vivo Studies ◽

Pc3 Cells ◽

Turnover Markers ◽

Induced Apoptosis

61 Background: The Src and IGF-1R axes are aberrantly activated in both PCa and the microenvironment of bone metastases. Dasatinib and BMS-754807 are clinically promising small molecule inhibitors with high potency against Src family kinases (SFK) and IR/IGF-1R, respectively. Based on a phase I/II clinical trial in which 9/19 pts treated with docetaxel + dasatinib were increased in serum IGF-1 levels after one cycle, the aim of this study was to establish potential antitumor cooperativity of inhibiting both IGF-1R and Src in experimental PCa models in vitro and in mice. Methods: Inhibition of Src and IGF-1R pathways was accomplished by pharmacologic agents (dasatinib against Src and BMS-754807 against IR/IGF-1R) as well as by shRNA, in PC3 and LNCaP cells. In vivo studies were done after orthotopic and intratibial injection of PC3 cells in nude mice. Results: SFK inhibition decreased proliferation and migration of PCa cells whereas IGF-1R blockade induced apoptosis. All anti-tumor effects were enhanced by dual blockade. IGF-1 induced phosphorylation of Akt1 and 2. Only Akt 1 phosphorylation was decreased by dasatinib; whereas Akt 1 and 2 phosphorylation were completely abrogated by the combination. Dasatinib and BMS-754807 inhibited orthotopic in vivo tumor growth of PC3 cells more potently than either inhibitor alone. Similarly, intratibial tumor growth and bone destruction was significantly reduced with the drug combination, accompanied by a decrease in serum bone turnover markers alkaline phosphatase and N-telopeptide. Conclusions: Dual inhibition of Src and IGF-1R has greater anti-tumor effect in PCa cells compared to inhibiting either alone. In the presence of IGF-1, dasatinib and BMS-754807 are necessary to inhibit IGF-1-induced phosphorylation of Akt1 and 2 in tumor cells in culture. In intratibial models, decreased bone turnover markers in serum support the concept of targeting both the epithelial and bone microenvironment. The combination of dasatinib and BMS-754807 may be a rational therapeutic approach in PCa by blocking complementary processes of tumor growth and progression.

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