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Efficacy and Safety Study of Recombinant Endostatin Combined With Chemotherapy to Treat Advanced Colorectal Cancer

ABSTRACT: Studies suggest that the addition of antiangiogenic agents to conventional therapeutic strategies, e.g., chemotherapy, radiation, or other tumor-targeting agents, will increase clinical efficacy. For advanced colorectal cancer,the antiangiogenic agent bevacizumab has become an important treatment option and its combination with chemotherapy is now being one of the standard first line therapy. This phase II study was conducted to determine the efficacy and safety of another antiangiogenesis inhibitor rh-endostatin plus mFOLFOX6 in advanced colorectal cancer.

DISEASE(S): Colorectal Cancer,Colorectal Neoplasms

PROVIDER: 2120061 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Secondary bacterial infections (SBIs) exacerbate influenza-associated disease and mortality. Antimicrobial agents can reduce the severity of SBIs, but many have limited efficacy or cause adverse effects. Thus, new treatment strategies are needed. Kinetic models describing the infection process can help determine optimal therapeutic targets, the time scale on which a drug will be most effective, and how infection dynamics will change under therapy. To understand how different therapies perturb the dynamics of influenza infection and bacterial coinfection and to quantify the benefit of increasing a drug’s efficacy or targeting a different infection process, I analyzed data from mice treated with an antiviral, an antibiotic, or an immune modulatory agent with kinetic models. The results suggest that antivirals targeting the viral life cycle are most efficacious in the first 2 days of infection, potentially because of an improved immune response, and that increasing the clearance of infected cells is important for treatment later in the infection. For a coinfection, immunotherapy could control low bacterial loads with as little as 20 % efficacy, but more effective drugs would be necessary for high bacterial loads. Antibiotics targeting bacterial replication and administered 10 h after infection would require 100 % efficacy, which could be reduced to 40 % with prophylaxis. Combining immunotherapy with antibiotics could substantially increase treatment success. Taken together, the results suggest when and why some therapies fail, determine the efficacy needed for successful treatment, identify potential immune effects, and show how the regulation of underlying mechanisms can be used to design new therapeutic strategies. Model is encoded by Ruby and submitted to BioModels by Ahmad Zyoud

2020-04-02 | MODEL1812040005 | BioModels

Recombinant Human Endostatin in Combination With XELOX Therapy in Patient With Advanced Colorectal Cancer.

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Transcription profiling of human dermal endothelial cells treated with 200ng/ml human recombinant endostatin for 6h

Project description:Cells were treated with 200ng/ml human recombinant endostatin (Pichia Pastoris) for 6h at 37C with 5 % CO2 and 95 % humidity.

2007-04-25 | E-RZPD-20 | biostudies-arrayexpress

Transcription profiling of human dermal enothelial cells treated with 200ng/ml human recombinant endostatin (Pichia Pastoris)

Project description:Cells were treated with 200ng/ml human recombinant endostatin (Pichia Pastoris) for 6h at 37°C with 5 % CO2 and 95 % humidity.

2013-01-30 | E-RZPD-10 | biostudies-arrayexpress

TBCRC 018: Phase II study of iniparib in combination with irinotecan to treat progressive triple negative breast cancer brain metastases

Project description:Approximately half of women diagnosed with advanced triple negative breast cancer (TNBC) will develop brain metastases, of which the majority will have uncontrolled extracranial disease. While local therapies to treat brain metastases are standardly prescribed, survival remains less than 6 months. This phase II, multi-center trial evaluated efficacy of irinotecan and iniparib, anti-cancer agents with activity in TNBC and known to cross the blood brain barrier, among 34 patients with new or progressive TNBC brain metastases. While time to progression was short (2.1 months), 27% of patients experienced intracranial clinical benefit and therapy was well-tolerated. Correlative studies illustrate partial response was associated with germline BRCA mutation status and high tumor expression of proliferation genes and signatures. To our knowledge, this is the first study showing feasibility of enrolling patients with progressive TNBC brain metastases to a systemic therapy and lays the groundwork for future studies to treat this devastating disease.

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Project description:We have witnessed the rise and fall of antiangiogenic therapy in breast cancer (BC). Nevertheless, clinical remissions were observed in patients and we were interested in studying the activity of antiangiogenic drugs in BC. Inefficacy of sunitinib was observed in mouse models of metastatic BC, where evidence of enhanced metastasis was reported, and lack of efficacy of sunitinib-docetaxel combination was recently reported in a phase III clinical trial. Our aim was to understand the mechanisms and predictors of response to sunitinib in BC in a cohort of patients with untreated locally advanced or operable BC treated with an upfront window of single agent sunitinib, followed by the combination of sunitinib and docetaxel. We have used microarray profiing to monitor the transcriptional changes associated with three distinct stages of treatment: at diagnosis and prior to any treatment (t1), after an upfront window of single agent sunitinib (t2) and after the combined treatment of sunitinib and docetaxel (t3). In addtion, this microarray data also allowed us to observe the transcriptional changes associated with primary resistance to angiogenic therapy in 4 of 12 patients likely mediated by an adaptive transcriptional response to hypoxia in these resistant tumors. In BC patients this is the first demonstration of primary resistance to antiangiogenic therapy.

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Transcriptome analysis of molecular mechanism in inhibition of x-ray or carbon-ion induced lung fibrosis by Fc-Endostatin and its derived peptides

Project description:Endostatin is a naturally occurring 183-amino acid proteolytic fragment of collagen XVIII that localizes in the basement membrane around blood vessels. The anti-tumor properties of this protein have been extensively described, demarcating endostatin as an endogenous inhibitor of angiogenesis. Further, it supresses many signaling cascades such as pro-inflammatory NF-κB, coagulation and adhesion cascades. Yamaguchi et al. reported that endostatin via its C-terminal domain (E4 peptide) has elicit anti-fibrosis effects. However, the zinc binding domain has been previously confined to the N terminus (endostatin mP1 peptide) and was critical to numerous functions of the molecule. The present study aimed to better understand the impact of oligomerization (Fc-Endostatin) as well as N- vs. C-terminal fragments of endostatin (mP1, CE4) on modulating radiation-induced lung fibrosis. Mice were treated with Fc-endostatin (Fc-Endo), N-terminus endostatin peptide (mP1) or C-terminus endostatin E4 peptide (CE4) combined with photon 20 Gy or carbon-ions 12.5 Gy whole thoracic irradiation

2023-11-09 | E-MTAB-6414 | biostudies-arrayexpress

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Project description:Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with a poor prognosis. Patients are typically diagnosed at an advanced stage due to the disease's long incubation period. Limited therapeutic advancements in the last two decades have prompted further investigation into alternative treatments. Previous studies have identified significant dysregulation in the mitotic spindle assembly checkpoint pathway and microtubule network of MPM, underscoring the potential of targeting microtubules in managing MPM. Deoxypodophyllotoxin (DPT) is a novel microtubule-targeting drug that has demonstrated promising therapeutic efficacy in various cancers. While the precise mechanism of DPT's anti-MPM effect remains undisclosed, our research indicates that DPT inhibits MPM growth in a dose-dependent manner both in vitro and in vivo. Moreover, it exhibits a favorable safety profile and shows lower toxicity towards normal cells and mice at therapeutic doses. Mechanistic studies involving three MPM cell lines (MSTO-211H, H2452, and H28) revealed that DPT induces multinucleated and micronucleated cells, disrupts spindle formation, and triggers Mitosis cell cycle arrest and necroptosis in tumor cells. In conclusion, our findings suggest that DPT holds promise as a safe and effective therapeutic option for MPM.

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