• 제목/요약/키워드: Preclinical trials

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The G115 standardized ginseng extract: an example for safety, efficacy, and quality of an herbal medicine

  • Bilia, Anna R.;Bergonzi, Maria C.
    • Journal of Ginseng Research
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    • 제44권2호
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    • pp.179-193
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    • 2020
  • Ginseng products on the market show high variability in their composition and overall quality. This becomes a challenge for both consumers and health-care professionals who are in search of high-quality, reliable ginseng products that have a proven safety and efficacy profile. The botanical extract standardization is of crucial importance in this context as it determines the reproducibility of the quality of the product that is essential for the evaluation of effectiveness and safety. This review focuses on the well-characterized and standardized ginseng extract, G115, which represents an excellent example of an herbal drug preparation with constant safety and efficacy within the herbal medicinal products. Over the many decades, extensive preclinical and clinical research has been conducted to evaluate the efficacy and safety of G115. In vitro and in vivo studies of G115 have shown pharmacological effects on physical performance, cognitive function, metabolism, and the immune system. Furthermore, a significant number of G115 clinical studies, most of them double-blind placebo-controlled, have reinforced the findings of preclinical evidence and proved the efficacy of this extract on blood glucose and lipid regulation, chronic obstructive pulmonary disease, energy, physical performance, and immune and cognitive functions. Clinical trials and 50 years of presence on the market are proof of a good safety profile of G115.

Magnetic Resonance-Guided Focused Ultrasound : Current Status and Future Perspectives in Thermal Ablation and Blood-Brain Barrier Opening

  • Lee, Eun Jung;Fomenko, Anton;Lozano, Andres M.
    • Journal of Korean Neurosurgical Society
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    • 제62권1호
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    • pp.10-26
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    • 2019
  • Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging new technology with considerable potential to treat various neurological diseases. With refinement of ultrasound transducer technology and integration with magnetic resonance imaging guidance, transcranial sonication of precise cerebral targets has become a therapeutic option. Intensity is a key determinant of ultrasound effects. High-intensity focused ultrasound can produce targeted lesions via thermal ablation of tissue. MRgFUS-mediated stereotactic ablation is non-invasive, incision-free, and confers immediate therapeutic effects. Since the US Food and Drug Administration approval of MRgFUS in 2016 for unilateral thalamotomy in medication-refractory essential tremor, studies on novel indications such as Parkinson's disease, psychiatric disease, and brain tumors are underway. MRgFUS is also used in the context of blood-brain barrier (BBB) opening at low intensities, in combination with intravenously-administered microbubbles. Preclinical studies show that MRgFUS-mediated BBB opening safely enhances the delivery of targeted chemotherapeutic agents to the brain and improves tumor control as well as survival. In addition, BBB opening has been shown to activate the innate immune system in animal models of Alzheimer's disease. Amyloid plaque clearance and promotion of neurogenesis in these studies suggest that MRgFUS-mediated BBB opening may be a new paradigm for neurodegenerative disease treatment in the future. Here, we review the current status of preclinical and clinical trials of MRgFUS-mediated thermal ablation and BBB opening, described their mechanisms of action, and discuss future prospects.

Garlic powder intake and cardiovascular risk factors: a meta-analysis of randomized controlled clinical trials

  • Kwak, Jin Sook;Kim, Ji Yeon;Paek, Ju Eun;Lee, You Jin;Kim, Haeng-Ran;Park, Dong-Sik;Kwon, Oran
    • Nutrition Research and Practice
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    • 제8권6호
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    • pp.644-654
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    • 2014
  • BACKGROUND/OBJECTIVES: Although preclinical studies suggest that garlic has potential preventive effects on cardiovascular disease (CVD) risk factors, clinical trials and reports from systematic reviews or meta-analyses present inconsistent results. The contradiction might be attributed to variations in the manufacturing process that can markedly influence the composition of garlic products. To investigate this issue further, we performed a meta-analysis of the effects of garlic powder on CVD risk factors. MATERIALS/METHODS: We searched PubMed, Cochrane, Science Direct and EMBASE through May 2014. A random-effects meta-analysis was performed on 22 trials reporting total cholesterol (TC), 17 trials reporting LDL cholesterol (LDL-C), 18 trials reporting HDL cholesterol (HDL-C), 4 trials reporting fasting blood glucose (FBG), 9 trials reporting systolic blood pressure (SBP) and 10 trials reporting diastolic blood pressure (DBP). RESULTS: The overall garlic powder intake significantly reduced blood TC and LDL-C by -0.41 mmol/L (95% confidence interval [CI], -0.69, -0.12) (-15.83 mg/dL [95% CI, -26.64, -4.63]) and -0.21 mmol/L (95% CI, -0.40, -0.03) (-8.11 mg/dL [95% CI, -15.44, -1.16]), respectively. The mean difference in the reduction of FBG levels was -0.96 mmol/L (95% CI, -1.91, -0.01) (-17.30 mg/dL [95% CI, -34.41, -0.18]). Evidence for SBP and DBP reduction in the garlic supplementation group was also demonstrated by decreases of -4.34 mmHg (95% CI, -8.38, -0.29) and -2.36 mmHg (95% CI, -4.56, -0.15), respectively. CONCLUSIONS: This meta-analysis provides consistent evidence that garlic powder intake reduces the CVD risk factors of TC, LDL-C, FBG and BP.

Concurrent Chemoradiation with Weekly Gemcitabine and Cisplatin for Locally Advanced Cervical Cancer

  • Hashemi, Farnaz Amouzegar;Akbari, Ehsan Hamed;Kalaghchi, Bita;Esmati, Ebrahim
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권9호
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    • pp.5385-5389
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    • 2013
  • Background: For more than 80 years, the standard treatment of locally advanced cervical cancer was radiotherapy. However, based on several phase III randomized clinical trials in the past decade, concurrent cisplatin-based chemoradiotherapy is the current standard for this disease. Gemcitabine has potent radiosensitizing properties in preclinical and clinical trials, so it can be utilized simultanously with radiation. Materials and Methods: Thirty women with untreated invasive squamous cell carcinoma of the cervix of stage IIB to stage IVA were enrolled in the study in the Radiation Oncology Department of Imam Khomeini Hospital in Tehran from September 2009 to September 2010. Sixty $mg/m^2$ gemcitabine followed by $35mg/m^2$ cisplatin were concurrently administered with radiotherapy to the whole pelvic region on day one of each treatment week for five weeks. One and three months after treatment, patients underwent a complete physical examination and MRI to determine the response to treatment. Results: The mean age of patients was $58.1{\pm}11.8$ (29-78) years. After 3 months of treatment, 73.3%had complete and 26.7% demonstrated partial response to treatment. Grade 3 anemia was seen in 10%, grade 3 thrombocytopenia in 3.3% and grade 3 leukopenia in 10% of the patients. Conclusions: According to the positive results of this study in stage IIB, further phase II and III clinical trials are suggested to evaluate the role of chemoradiation using Gemcitabine for advanced cervical cancers.

Clinical and preclinical tolerance protocols for vascularized composite allograft transplantation

  • Yang, Jerry Huanda;Johnson, Ariel C.;Colakoglu, Salih;Huang, Christene A.;Mathes, David Woodbridge
    • Archives of Plastic Surgery
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    • 제48권6호
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    • pp.703-713
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    • 2021
  • The field of vascularized composite allografts (VCAs) has undergone significant advancement in recent decades, and VCAs are increasingly common and accepted in the clinical setting, bringing hope of functional recovery to patients with debilitating injuries. A major obstacle facing the widespread application of VCAs is the side effect profile associated with the current immunosuppressive regimen, which can cause a wide array of complications such as infection, malignancy, and even death. Significant concerns remain regarding whether the treatment outweighs the risk. The potential solution to this dilemma would be achieving VCA tolerance, which would allow recipients to receive allografts without significant immunosuppression and its sequelae. Promising tolerance protocols are being studied in kidney transplantation; four major trials have attempted to withdraw immunosuppressive treatment with various successes. The common theme in all four trials is the use of radiation treatment and donor cell transplantation. The knowledge gained from these trials can provide valuable insight into the development of a VCA tolerance protocol. Despite similarities, VCAs present additional barriers compared to kidney allografts regarding tolerance induction. VCA donors are likely to be deceased, which limits the time for significant pre-conditioning. VCA donors are also more likely to be human leukocyte antigen-mismatched, which means that tolerance must be induced across major immunological barriers. This review also explores adjunct therapies studied in large animal models that could be the missing element in establishing a safe and stable tolerance induction method.

Ongoing Clinical Trials of Vaccines to Fight against COVID-19 Pandemic

  • Chiranjib Chakraborty;Ashish Ranjan Sharma;Manojit Bhattacharya;Garima Sharma;Rudra P. Saha;Sang-Soo Lee
    • IMMUNE NETWORK
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    • 제21권1호
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    • pp.5.1-5.22
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    • 2021
  • Coronavirus disease 2019 (COVID-19) has developed as a pandemic, and it created an outrageous effect on the current healthcare and economic system throughout the globe. To date, there is no appropriate therapeutics or vaccines against the disease. The entire human race is eagerly waiting for the development of new therapeutics or vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Efforts are being taken to develop vaccines at a rapid rate for fighting against the ongoing pandemic situation. Amongst the various vaccines under consideration, some are either in the preclinical stage or in the clinical stages of development (phase-I, -II, and -III). Even, phase-III trials are being conducted for some repurposed vaccines like Bacillus Calmette-Guérin, polio vaccine, and measles-mumps-rubella. We have highlighted the ongoing clinical trial landscape of the COVID-19 as well as repurposed vaccines. An insight into the current status of the available antigenic epitopes for SARS-CoV-2 and different types of vaccine platforms of COVID-19 vaccines has been discussed. These vaccines are highlighted throughout the world by different news agencies. Moreover, ongoing clinical trials for repurposed vaccines for COVID-19 and critical factors associated with the development of COVID-19 vaccines have also been described.

Radiotherapy and immune checkpoint blockades: a snapshot in 2016

  • Koo, Taeryool;Kim, In Ah
    • Radiation Oncology Journal
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    • 제34권4호
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    • pp.250-259
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    • 2016
  • Immune checkpoint blockades including monoclonal antibodies (mAbs) of cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) have been emerged as a promising anticancer therapy. Several immune checkpoint blockades have been approved by US Food and Drug Administration (FDA), and have shown notable success in clinical trials for patients with advanced melanoma and non-small cell lung cancer. Radiotherapy is a promising combination partner of immune checkpoint blockades due to its potent pro-immune effect. This review will cover the current issue and the future perspectives for combined with radiotherapy and immune checkpoint blockades based upon the available preclinical and clinical data.

Emerging Co-signaling Networks in T Cell Immune Regulation

  • Jung, Keunok;Choi, Inhak
    • IMMUNE NETWORK
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    • 제13권5호
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    • pp.184-193
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    • 2013
  • Co-signaling molecules are surface glycoproteins that positively or negatively regulate the T cell response to antigen. Co-signaling ligands and receptors crosstalk between the surfaces of antigen-presenting cells (APCs) and T cells, and modulate the ultimate magnitude and quality of T cell receptor (TCR) signaling. In the past 10 years, the field of co-signaling research has been advanced by the understanding of underlying mechanisms of the immune modulation led by newly identified co-signaling molecules and the successful preclinical and clinical trials targeting co-inhibitory molecules called immune checkpoints in the treatment of autoimmune diseases and cancers. In this review, we briefly describe the characteristics of well-known B7 co-signaling family members regarding the expression, functions and therapeutic implications and to introduce newly identified B7 members such as B7-H5, B7-H6, and B7-H7.

Comparative Proteome Analysis of Celastrol-Treated Helicobacter pylori

  • Kim, Sa-Hyun
    • 대한의생명과학회지
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    • 제23권4호
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    • pp.395-401
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    • 2017
  • Various preclinical and clinical trials have been conducted the efficacy of celastrol. In data presented in the current manuscript is the first trial to inhibit Helicobacter pylori with celastrol. In this study, the quantitative change of various H. pylori proteins including CagA and VacA by the anti-bacterial effect of celastrol was determined. The anti-H. pylori effects of celastrol was investigated by performing 2-dimensional electrophoresis and additional supporting experiments. After 2-dimensional electrophoresis analysis, spot intensities were analyzed and then each spot was identified using matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) or peptide sequencing using Finnigan LCQ ion trap mass spectrometer (LC-MS/MS). The results show that celastrol has multiple effects on protein expression in H. pylori.

Human Tumor Xenograft Models for Preclinical Assessment of Anticancer Drug Development

  • Jung, Joohee
    • Toxicological Research
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    • 제30권1호
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    • pp.1-5
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    • 2014
  • Xenograft models of human cancer play an important role in the screening and evaluation of candidates for new anticancer agents. The models, which are derived from human tumor cell lines and are classified according to the transplant site, such as ectopic xenograft and orthotopic xenograft, are still utilized to evaluate therapeutic efficacy and toxicity. The metastasis model is modified for the evaluation and prediction of cancer progression. Recently, animal models are made from patient-derived tumor tissue. The patient-derived tumor xenograft models with physiological characters similar to those of patients have been established for personalized medicine. In the discovery of anticancer drugs, standard animal models save time and money and provide evidence to support clinical trials. The current strategy for using xenograft models as an informative tool is introduced.