A Parenteral Econazole Formulation Using a Novel Micelle-to-Liposome Transfer Method: In Vitro Characterization and Tumor Growth Delay in a Breast Cancer Xenograft Model

2006 ◽  
Vol 23 (11) ◽  
pp. 2575-2585 ◽  
Author(s):  
Sebastian Cogswell ◽  
Stuart Berger ◽  
Dawn Waterhouse ◽  
Marcel B. Bally ◽  
Ellen K. Wasan
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Xenograft Model ◽  
Growth Delay ◽  
Tumor Growth Delay ◽  
Breast Cancer Xenograft ◽  
In Vitro Characterization ◽  
Transfer Method

scholarly journals Edelfosine nanoemulsions inhibit tumor growth of triple negative breast cancer in zebrafish xenograft model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sofia M. Saraiva ◽  
Carlha Gutiérrez-Lovera ◽  
Jeannette Martínez-Val ◽  
Sainza Lores ◽  
Belén L. Bouzo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Xenograft Model ◽  
Skin Barrier ◽  
Zebrafish Embryos ◽  
Biorelevant Media

AbstractTriple negative breast cancer (TNBC) is known for being very aggressive, heterogeneous and highly metastatic. The standard of care treatment is still chemotherapy, with adjacent toxicity and low efficacy, highlighting the need for alternative and more effective therapeutic strategies. Edelfosine, an alkyl-lysophospholipid, has proved to be a promising therapy for several cancer types, upon delivery in lipid nanoparticles. Therefore, the objective of this work was to explore the potential of edelfosine for the treatment of TNBC. Edelfosine nanoemulsions (ET-NEs) composed by edelfosine, Miglyol 812 and phosphatidylcholine as excipients, due to their good safety profile, presented an average size of about 120 nm and a neutral zeta potential, and were stable in biorelevant media. The ability of ET-NEs to interrupt tumor growth in TNBC was demonstrated both in vitro, using a highly aggressive and invasive TNBC cell line, and in vivo, using zebrafish embryos. Importantly, ET-NEs were able to penetrate through the skin barrier of MDA-MB 231 xenografted zebrafish embryos, into the yolk sac, leading to an effective decrease of highly aggressive and invasive tumoral cells’ proliferation. Altogether the results demonstrate the potential of ET-NEs for the development of new therapeutic approaches for TNBC.

TRU-016, An Anti-CD37 SMIP™ Biologic, In Combination with Other Therapeutic Drugs In Models of Non-Hodgkin's Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3931-3931 ◽  
Author(s):  
Paul A. Algate ◽  
Jennifer Wiens ◽  
Christy Nilsson ◽  
Mien Sho ◽  
Debra T. Chao ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Cell Lymphoma ◽  
Combination Index ◽  
Growth Delay ◽  
Tumor Growth Delay ◽  
B Cell Malignancies

Abstract Abstract 3931 Background: CD37 is a 50–55 kDa heavily glycosylated member of the tetraspanin superfamily of molecules. This cell surface protein is expressed on normal and transformed B-cells, and has been implicated in diverse processes including cellular activation and proliferation, cell motility, and cell-cell adhesion. TRU-016 is a novel humanized anti-CD37 SMIP™ protein. Pre-clinical studies have demonstrated that anti-CD37 SMIP™ protein mediates caspase-independent direct killing of normal and malignant B-cells, a mechanism of action that appears to be different than CD20 therapies. In addition, TRU-016 results in indirect killing through NK cell mediated SMIP-protein directed cellular cytotoxicity (SDCC). The therapeutic potential of TRU-016 against several subsets of B-cell malignancies is currently being investigated in the clinic. Methods: The ability of TRU-016 to interact and increase cell killing with established therapeutics rituximab (anti-CD20 antibody), bendamustine (bi-functional alkylating agent/nucleoside analog), LY294002 (PI3K inhibitor) and temsirolimus (mTOR inhibitor) was investigated in vitro using the Rec-1 (mantle cell lymphoma) and SU-DHL-6 (diffuse large B cell lymphoma) cell lines. Individual drugs were tested in combination with TRU-016 as well as in a multiple drug cocktail. Combination index analyses were performed for drug combinations over the 20–90% effect levels. To determine whether in vitro synergy could be recapitulated in vivo, DoHH-2 (follicular lymphoma) xenografts were treated with TRU-016, bendamustine, and the combination of TRU-016 and bendamustine with or without rituximab. Furthermore, the effect of the dosing schedule with the combination of TRU-016 and rituximab was explored by comparing the treatment over a short time period to an extended (maintenance) dosing regimen. CD37 expression on the tumor xenografts was evaluated post different treatment by immunohistochemistry. Results: Combination index analyses determined that the killing effects of TRU-016 was synergistic with rituximab, bendamustine and temsirolimus in NHL models. Furthermore, TRU-016 provided additional efficacy when added to the combination of rituximab and bendamustine. In vivo results demonstrated that the in vitro synergy results were applicable to a more complex in vivo disease model. The combination of TRU-016 with bendamustine or rituximab resulted in increased tumor growth delay compared to that attained with the individual drugs. The addition of TRU-016 to the combination of bendamustine and rituximab resulted in increased tumor growth delay compared to the two drugs alone. The observed efficacy of the combination of TRU-016 and rituximab could be extended with repeated (maintenance) dosing with tumor free survival being observed beyond the 35 days of dosing. The combination of TRU-016 with temsirolimus also resulted in a reduction of tumor growth compared to either molecule alone. CD37 target expression was detected in the xenograft tumors post-treatment with all drugs tested. Conclusions: TRU-016 in combination with rituximab, bendamustine or temsirolimus increased cell killing of NHL cells in vitro over that observed for each agent alone. Furthermore, the triple combination of TRU-016 with rituximab, bendamustine or temsirolimus displayed greater anti-tumor activity in vivo than each of the agents alone against a follicular lymphoma tumor model. The addition of TRU-016 to a combination of rituximab and bendamustine resulted in increased killing in vitro and in vivo. The combinatorial activity of TRU-016 and rituximab in vivo was increased when the drugs were administered over a longer period. These results provide preclinical rationale for the potential different combinations of TRU-016 with several established therapeutics for the treatment of NHL and related B-cell malignancies. Disclosures: Algate: Trubion Pharmaceuticals: Employment. Wiens:Trubion Pharmaceuticals: Employment. Nilsson:Trubion Pharmaceuticals: Employment. Sho:Facet/Abbott: Employment. Chao:Facet/Abbott: Employment. Starling:Facet/Abbott: Employment. Gordon:Trubion Pharmaceuticals: Employment.

scholarly journals Cordycepin-enriched Cordyceps militaris induces immunomodulation and tumor growth delay in mouse-derived breast cancer

2013 ◽  
Vol 30 (4) ◽  
pp. 1996-2002 ◽  
Author(s):  
MIN-HO JEONG ◽  
CHANG-MIN LEE ◽  
SANG-WHA LEE ◽  
SU-YEONG SEO ◽  
MIN-JEONG SEO ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cordyceps Militaris ◽  
Growth Delay ◽  
Tumor Growth Delay

Darbepoetin alfa Radiosensitizes Tumors Independent of Anemia or the Correction of Anemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1637-1637
Author(s):  
Shoucheng Ning ◽  
Sinclair Angus ◽  
Hartley Cynthia ◽  
Knox Susan4
Keyword(s):  
Tumor Growth ◽  
Tumor Cells ◽  
Fold Increase ◽  
Growth Delay ◽  
Local Tumor ◽  
Tumor Growth Delay ◽  
Tumor Bearing ◽  
Tumor Irradiation

Abstract Darbepoetin alfa (DA) is a FDA approved long acting erythropoietic protein. We hypothesized that correction of anemia in tumor-bearing mice by DA would secondarily increase the tumor pO2 and potentiate radiation-induced cell killing of tumor cells. To test this hypothesis, we used total body irradiation (TBI) to induce anemia in C3H mice. Murine squamous cell carcinoma tumor (SCC VII) and fibrosarcoma (RIF-1) models were used to study tumor responses to radiation in vivo. DA (30μg/kg) was administered i.p. either every two weeks or weekly. EPO-R RNA levels were measured in tumors from normal, anemic and DA treated mice in both tumor models. Tumors were locally irradiated with daily fractions of 250 cGy for 5 days. Following 500 cGy TBI, hemoglobin levels decreased and reached a nadir of 7.0 ± 0.9 gm/dL 14 days post TBI. Administration of DA reduced the depth and duration of anemia and improved the general health condition of anemic animals as evidenced by accelerated recovery of body weight following the TBI and maintenance of normal levels of activity compared to similarly irradiated animals not treated with DA. Mice treated with DA on the same day as the TBI had elevated hemoglobin levels with a nadir of 11.1 gm/dL on day 14 after TBI. Systemic administration of DA alone did not stimulate tumor growth in TBI-induced anemic mice. When combined with fractionated local tumor irradiation, administration of DA at any of the time points studied (18, 11, 4 and 0 days before initiation of local tumor irradiation) delayed tumor growth and increased the tumor growth delay time from 2.7 days for irradiation alone to 7.3 – 10.6 days for DA treated animals (p < 0.01). There was no statistically significant difference between tumor growth delay times for groups of mice treated with DA at various times before tumor irradiation. Although DA effectively corrected anemia in tumor-bearing mice and significantly decreased the number of hypoxic cells in the tumors as shown by EF5 staining, radiosensitization by DA was independent of the correction of anemia. EPOR RNA expression was barely detectible in tumors cultured in vitro. There were no differences in EPO-R RNA levels in tumors from anemic or DA treated mice (1–2 fold increase), although EPO-R transcription was upregulated in tumors grown in vivo compared to control tumors lines grown in vitro (40–80 fold increase). This may be due to hypoxic induction of EPO-R by tumors in vivo or expression of EPO-R by endothelial cells or infiltrating macrophages. Results from an experiment in non-anemic mice with RIF-1 tumors suggest that DA can sensitize tumor cells in non-anemic mice to radiation as well. These results support the idea that radiosensitization by DA is independent of hemoglobin and tumor pO2. It has long been assumed that anemia causes decreased tumor oxygenation and increased tumor radioresistance, and that correction of anemia would therefore increase tumor pO2, and result in enhanced radiosensitivity. However, the data presented here challenge this presumed relationship. These findings are promising and may have relevance to the treatment of patients with a variety of tumor types with radiation therapy.

Dichloroacetate induces tumor-specific radiosensitivity in vitro but attenuates radiation-induced tumor growth delay in vivo

2013 ◽  
Vol 189 (8) ◽  
pp. 684-692 ◽  
Author(s):  
F. Zwicker ◽  
A. Kirsner ◽  
P. Peschke ◽  
F. Roeder ◽  
J. Debus ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Growth Delay ◽  
Tumor Growth Delay ◽  
Radiation Induced

In vitro and in vivo antitumor activities of a small and novel synthetic molecule: A potential therapy for hepatocellular carcinoma.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 300-300
Author(s):  
K. I. Batarseh
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Therapeutic Potential ◽  
Statistical Tests ◽  
Xenograft Model ◽  
Growth Delay ◽  
Antitumor Activities ◽  
Immunodeficient Mice

300 Background: A small (molecular weight of 275) and novel pharmaceutically silver (I)-tartaric acid complex given the title name aliargentumycine was recently synthesized and the results on its in vitro cytotoxicity and mechanism of action on solid and hematopoietic malignancies were reported. Here the therapeutic potential of aliargentumycine on hepatocellular carcinoma was investigated. Methods: The in vitro and in vivo antitumor activities of aliargentumycine were studied on human HepG-2 xenograft model grown subcutaneously in female immunodeficient mice. Aliargentumycine was administered intratumorally, intravenously and orally twice a week at various concentrations. Results: The IC50 of aliargentumycine was found to be 1.49 ± 0.067 mg/ml, which is comparable to the value of 1.04 ± 0.07 mg/ml for doxorubicin, and almost half the value of 2.87 ± 1.02 mg/ml for sorafenib tosylate. The in vivo results demonstrated excellent statistically significant antitumor activities for the intratumoral, intravenous and oral routes of administration with Pi.t. < 0.00001, Pi.v. < 0.005 and Pp.o. < 0.003, respectively. Some animals showed complete tumor remission (tumor-free), and no tumor re-growth was observed even after treatment was stopped. Nonlinear regression on the data revealed that aliargentumycine results in significant tumor growth delay. All treated animals did not show any commonly observed signs of toxicity, including no body weight loss (p > 0.05). Mantel-Cox statistical tests revealed that there were significant tumor growth delays (p < 0.05) and survival advantages (p < 0.05). Conclusions: These promising findings might have great therapeutic potential on the future clinical treatment of hepatocellular carcinoma using aliargentumycine. No significant financial relationships to disclose.

Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

2019 ◽  
Vol 2 (4) ◽  
pp. 83-98 ◽  
Author(s):  
André De Lima Mota ◽  
Bruna Vitorasso Jardim-Perassi ◽  
Tialfi Bergamin De Castro ◽  
Jucimara Colombo ◽  
Nathália Martins Sonehara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucose Metabolism ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Carbonic Anhydrases ◽  
In Vivo Models ◽  
Ca Ix ◽  
Gene And Protein Expression

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression. 

scholarly journals Cytotoxic effects and tolerability of gemcitabine and axitinib in a xenograft model for c-myc amplified medulloblastoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stefanie Schwinn ◽  
Zeinab Mokhtari ◽  
Sina Thusek ◽  
Theresa Schneider ◽  
Anna-Leena Sirén ◽  
...  
Keyword(s):  
Fluorescence Microscopy ◽  
Tumor Growth ◽  
Intensive Therapy ◽  
Xenograft Model ◽  
Light Sheet ◽  
Tumor Control ◽  
Orthotopic Model ◽  
Group 3 ◽  
Light Sheet Fluorescence Microscopy

AbstractMedulloblastoma is the most common high-grade brain tumor in childhood. Medulloblastomas with c-myc amplification, classified as group 3, are the most aggressive among the four disease subtypes resulting in a 5-year overall survival of just above 50%. Despite current intensive therapy regimens, patients suffering from group 3 medulloblastoma urgently require new therapeutic options. Using a recently established c-myc amplified human medulloblastoma cell line, we performed an in-vitro-drug screen with single and combinatorial drugs that are either already clinically approved or agents in the advanced stage of clinical development. Candidate drugs were identified in vitro and then evaluated in vivo. Tumor growth was closely monitored by BLI. Vessel development was assessed by 3D light-sheet-fluorescence-microscopy. We identified the combination of gemcitabine and axitinib to be highly cytotoxic, requiring only low picomolar concentrations when used in combination. In the orthotopic model, gemcitabine and axitinib showed efficacy in terms of tumor control and survival. In both models, gemcitabine and axitinib were better tolerated than the standard regimen comprising of cisplatin and etoposide phosphate. 3D light-sheet-fluorescence-microscopy of intact tumors revealed thinning and rarefication of tumor vessels, providing one explanation for reduced tumor growth. Thus, the combination of the two drugs gemcitabine and axitinib has favorable effects on preventing tumor progression in an orthotopic group 3 medulloblastoma xenograft model while exhibiting a favorable toxicity profile. The combination merits further exploration as a new approach to treat high-risk group 3 medulloblastoma.

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