Prospective single-arm clinical study of TBC as conditioning regimen for haplo-identical hematopoietic stem cell transplantation in refractory / relapsed acute myeloid leukemia

开始日期2022-11-08

申办/合作机构-

NCT03050814

/ Terminated临床2期IIT

A Randomized Phase II Trial of Standard of Care Alone or in Combination With Ad-CEA Vaccine and Avelumab in Patients With Previously Untreated Metastatic or Unresectable Colorectal Cancer

Background:
Colorectal cancer is a common cancer in the Unites States (U.S.) It causes the second most cancer-related deaths. The drug avelumab and vaccine Ad-CEA together help the immune system fight cancer.
Objective:
To test if avelumab and Ad-CEA plus standard therapy treats colorectal cancer that has spread to other sites better than standard therapy alone.
Eligibility:
People ages 18 and older with untreated colorectal cancer that has spread in the body
Design:
Participants will be screened with:
Test to see if their cancer has a certain deficiency
Blood, urine, and heart tests
Scans
Medical history
Physical exam
Tumor sample. This can be from a previous procedure.
A small group of participants will get Ad-CEA and avelumab plus standard therapy. This is leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX) plus bevacizumab for up to 24 weeks then capecitabine plus bevacizumab.
The others will have treatment in 2-week cycles. They will be Arm A or B:
Arm A: FOLFOX and bevacizumab by intravenous (IV) days 1 and 2 for 12 cycles. After that, capecitabine by mouth twice a day and bevacizumab by IV on day 1.
Arm B: Ad-CEA injection every 2-12 weeks. Avelumab by IV on day 1 of each cycle. FOLFOX and bevacizumab by IV days 2 and 3 for 12 cycles. Then, capecitabine by mouth twice a day and bevacizumab through IV on day 2.
Participants will repeat screening tests during the study.
Participants will be treated until their disease gets worse or they have bad side effects. Arm A participants can join Arm B. They will have a visit 4 5 weeks after they stop therapy.

开始日期2017-04-05

申办/合作机构

National Cancer Institute

NCT00027833

/ Unknown status临床2期IIT

Pilot Phase II Study of Safety and Immunogenicity of an ALVAC-CEA/B7.1 Vaccine Administered With Chemotherapy, Alone or in Combination With Tetanus Toxoid, as Compared to Chemotherapy Alone, in Patients With Metastatic Colorectal Adenocarcinoma

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Tetanus toxoid may make tumor cells more sensitive to chemotherapy and vaccine therapy.
PURPOSE: Randomized phase II trial to study the effectiveness of chemotherapy and vaccine therapy with or without tetanus toxoid compared with chemotherapy alone in treating patients who have metastatic colorectal cancer.

开始日期2001-12-01

申办/合作机构

The Herbert Irving Comprehensive Cancer Center

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100 项与 Recombinant canarypox virus-based vaccine(Therion Biologics Corp.) 相关的临床结果

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100 项与 Recombinant canarypox virus-based vaccine(Therion Biologics Corp.) 相关的转化医学

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100 项与 Recombinant canarypox virus-based vaccine(Therion Biologics Corp.) 相关的专利（医药）

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255

项与 Recombinant canarypox virus-based vaccine(Therion Biologics Corp.) 相关的文献（医药）

2025-05-01·Journal of Ethnopharmacology

The inhibition of PPARα protein degradation alleviates the cardiotoxicity of Tiebangchui by regulating fatty acid metabolism

Article

作者: Meng, Xianli ; Xu, Lei ; Zhou, Ruichen ; Liu, Yue ; Zhang, Yi ; Zhang, Tao ; Yang, Lu ; Liu, Xianfeng

ETHNOPHARMACOLOGICAL RELEVANCETiebangchui (TBC) is a traditional Tibetan medicine that is commonly used to relieve pain and inflammation in China. Nevertheless, the poisoning incidents of TBC have often been reported in clinical application, which severely limits the use of TBC. Therefore, the cardiotoxicity mechanism of TBC and the way of toxicity reduction need to be explored deeply, which are of great significance for clinical safety and reasonable medication.AIM OF THE STUDYThe aim of this study was to explore the cardiotoxicity mechanism of TBC.METHODSIn this study, the cardiotoxicity of TBC or its main components (aconitine (Aco), 3-deoxyaconitine (Deo)) on zebrafish and H9c2 cells were evaluated. And potential cardiotoxicity mechanism was screened by transcriptomics technology. Lipid levels and adenosine triphosphate (ATP) content was determined by biochemical kit or staining. Subsequently, quantitative Real-time PCR (qRT-PCR), Western blot and immunofluorescence were used to detect the expression level of relevant targets. In addition, we investigated the protective effect of peroxisome proliferator-activated receptor-α (PPARα) agonist (WY14643) against the cardiotoxicity induced by Deo and Aco in zebrafish and H9c2 cells. Molecular docking and cell thermal shift assay (CETSA) were used to determine the molecular binding capability between drugs and PPAR-α. Furthermore, co-immunoprecipitation (Co-IP) and protease inhibitors was employed to investigate the degradation mechanism of PPARα protein.RESULTSTBC and its main toxic components can cause cardiac function disorder and cardiac damage in zebrafish. Meantime, they can induce the apoptosis of cardiomyocytes, increase the accumulation of lipid and energy deficit both in vivo and in vitro. Further mechanism studies showed that the main toxic components can promote fatty acid absorption and inhibit fatty acid oxidation, thus resulting in lipid toxicity and insufficient energy production. After combined treatment with the PPARα agonist (WY14643), the cardiotoxicity of aconitine and 3-deoxyaconitine to zebrafish and H9c2 cells was significantly alleviated. Moreover, we found that aconitine and 3-deoxyaconitine can directly bind with PPARα protein and accelerate its ubiquitin-dependent degradation.CONCLUSIONTBC can induce cardiotoxicity by impairing fatty acid metabolism through accelerating PPARα ubiquitin-dependent degradation.

2025-04-01·Pest Management Science

Design, synthesis, molecular docking and antimicrobial evaluation of benzoylurea derivatives containing difluoromethyl (trifluoromethyl) pyrimidine

Article

作者: Yin, Rongxiu ; Fei, Qiang ; Wu, Wenneng ; Chen, Haijiang ; An, Jiansong ; Yang, Song ; Lan, Wenjun ; Xu, Su ; Yang, Lin‐Lin

AbstractBACKGROUNDThe reduction in agricultural product quality and yield caused by fungal and bacterial plant diseases has led to considerable economic losses in global crop production and poses a threat to human health. The primary method of control remains the use of chemical agents. In an effort to develop novel and highly effective antimicrobial agents, a series of benzoylurea derivatives incorporating a difluoromethyl (trifluoromethyl) pyrimidine structure were designed and synthesized.RESULTSIn this study, we designed and synthesized a series of novel benzoylurea derivatives containing difluoromethyl (trifluoromethyl) pyrimidine fragments. Several of the synthesized compounds exhibited notable antifungal activity in vitro against PS, CBC, BBC and TBC. Their efficacy surpassed that of the positive controls HM and Pyr. Notably, 6s demonstrated an EC50 value of 4.10 μg mL−1, significantly lower than the 31.25 μg mL−1 for Pyr. In antibacterial assays, 6s also showed an 87.49% inhibition rate against Xoc. Moreover, in vivo tests against CBC revealed a protective efficacy of 59.39% at a concentration of 25 μg mL−1. Molecular docking simulations further supported its strong activity. To explore the mechanism of action of 6s on CBC, we conducted scanning electron microscopy, succinate dehydrogenase enzyme assays, and measurements of dry weight, membrane permeability, cellular contents, and ROS.CONCLUSIONThis study underscores the potential of benzoylurea derivatives containing difluoromethyl (trifluoromethyl) pyrimidine fragments as lead compounds for the management of CBC. The results offer important insights and pave the way for the development of novel fungicides, contributing to improved crop protection strategies in agriculture. © 2024 Society of Chemical Industry.

2025-02-01·Food Chemistry

Role of red beetroot in bread for reducing mycotoxin risks: Bioavailability of beetroot polyphenols and betalains with ochratoxin a, aflatoxin B1 and zearalenone in Caco-2 cells

Article

作者: Ana, Juan-García ; Carlos, Moltó Juan ; Hannu, Pakkanen ; Eeva-Riikka, Vehniäinen ; Cristina, Juan ; Paula, Llorens

The interaction between dietary bioactive compounds and mycotoxins in food safety is crucial due to the potential health risks raised by mycotoxins and the protective functions of bioactive substances. This study is focused on red beetroot (Beta vulgaris), a rich source of polyphenols and betalains, incorporated into a daily consumption food such as bread, to examine its effects on the bioavailability of mycotoxins using an in vitro Caco-2 cell model. This study investigates how these compounds affect the bioavailability of mycotoxins, specifically ochratoxin A (OTA), aflatoxin B1 (AFB1), and zearalenone (ZEA), which are known to compromise intestinal barrier function and nutrient absorption. Additionally, bioaccesibility and bioavailability of total betalains (betacyanins and betaxanthins) (TBC) and polyphenols (TPC) content was evaluated. The beetroot-enriched breads were subjected to an in vitro digestion process, followed by a transepithelial transport assay to assess the bioavailability in differentiated Caco-2 cells. Results indicate an increase in the bioaccesibility of TBC and TPC (up to 99 % and 27 %, respectively) during digestion, suggesting enhanced absorption and protective effects against mycotoxin-induced damage. The presence of beetroot bread polyphenols and betalains increased the bioavailability of mycotoxins, with complex interactions observed, particularly in triple mycotoxin's combination. The results highlight the complex interactions between dietary components and mycotoxins' bioavailability, underlining the importance of further research into their mechanisms of action and potential applications in food safety and nutrition.

100 项与 Recombinant canarypox virus-based vaccine(Therion Biologics Corp.) 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
转移性结直肠癌	临床2期	加拿大	National Cancer Institute	2001-12-01
转移性结直肠癌	临床2期	加拿大	National Cancer Institute	2001-12-01
转移性结直肠癌	临床2期	美国	National Cancer Institute	2001-12-01
转移性结直肠癌	临床2期	美国	National Cancer Institute	2001-12-01
结直肠癌	临床2期	加拿大	Therion Biologics Corp.	-
结直肠癌	临床2期	美国	Sanofi Pasteur SA	-
结直肠癌	临床2期	美国	Therion Biologics Corp.	-
结直肠癌	临床2期	加拿大	Sanofi Pasteur SA	-
黑色素瘤	临床2期	-	Sanofi Pasteur SA	-
黑色素瘤	临床2期	-	Therion Biologics Corp.	-