• Title/Summary/Keyword: Preclinical trials

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The Effect of Germanium Complex on the Body Fat Weight, Body Weight and Serum Biochemical Value in Rats Fed High Fat Diets (게르마늄 복합물이 비만유도 흰쥐의 체지방 및 체중과 생화학적 변화에 미치는 영향)

  • Jung, Winston;Song, Si-Whan;Hong, Dong-Ho
    • YAKHAK HOEJI
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    • v.50 no.3
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    • pp.160-165
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    • 2006
  • Germanium is found in a range of minerals and ores and is present in foods including beans, tomato juice, oysters, tuna and garlic. Germanium is a non-metallic element, which can exist in valence states of 2 and 4. Clinical trials and use in private practices for more than a decade have demonstrated organic germanium's efficacy in treating serious disease including cancer, arthritis and senile osteoporosis. But it was rarely reported that inorganic germanium has biological properties. STB-BM contains mineral complex, rare earth elements and a little amount of Inorganic germanium. The experiment was carried out the anti-obesity effect. To investigate anti-obesity effect of STB-BM, we measured the effect of body weight, fat weight (subcutaneous fat, epididymal fat, visceral fat, kidney fat and total fat) and serum biochemical level in rats fed high fat diets. STB-BM 35 mg/kg suppressed the increasing ratio of body weight, epididymal fat weight, visceral fat weight, total fat weight, triglyceride and LDL-cholesterol (p<0.05).

Andrographolides and traditionally used Andrographis paniculata as potential adaptogens: Implications for therapeutic innovation

  • Thakur, Ajit Kumar;Chatterjee, Shyam Sunder;Kumar, Vikas
    • CELLMED
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    • v.4 no.3
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    • pp.15.1-15.14
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    • 2014
  • Andrographis paniculata (Burm. F.) Wall. Ex Nees (Family: Anthaceae) is a traditionally known Ayurvedic medicinal plant. Several well-controlled clinical trials conducted during recent years have consistently reconfirmed that Andrographis paniculata extracts are effective in suppressing cardinal symptoms of diverse inflammatory and infectious diseases. Despite extensive efforts though, many questions concerning bioactive constituents of such extracts and their modes of actions still remain unanswered. Amongst diverse diterpene lactones isolated to date from such extracts, andrographolide is often considered to be the major, representative, or bioactive secondary metabolite of the plant. Therefore, it has attracted considerable attention of several drug discovery laboratories as a lead molecule potentially useful for identifying structurally and functionally novel drug. Critical analysis of available preclinical and clinical information on Andrographis paniculata extracts and pure andrographolide strongly suggest that they are pharmacologically polyvalent and that they possess adaptogenic properties. Aim of this communication is to summarize and critically analyze such data, and to point out some possibilities for more rationally exploiting their adaptogenic properties for discovering novel therapeutic leads, or for obtaining pharmacologically better standardized phyto-pharmaceuticals.

Molecular Mechanisms of Apoptosis and Roles in Cancer Development and Treatment

  • Goldar, Samira;Khaniani, Mahmoud Shekari;Derakhshan, Sima Mansoori;Baradaran, Behzad
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2129-2144
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    • 2015
  • Programmed cell death (PCD) or apoptosis is a mechanism which is crucial for all multicellular organisms to control cell proliferation and maintain tissue homeostasis as well as eliminate harmful or unnecessary cells from an organism. Defects in the physiological mechanisms of apoptosis may contribute to different human diseases like cancer. Identification of the mechanisms of apoptosis and its effector proteins as well as the genes responsible for apoptosis has provided a new opportunity to discover and develop novel agents that can increase the sensitivity of cancer cells to undergo apoptosis or reset their apoptotic threshold. These novel targeted therapies include those targeting anti-apoptotic Bcl-2 family members, p53, the extrinsic pathway, FLICE-inhibitory protein (c-FLIP), inhibitor of apoptosis (IAP) proteins, and the caspases. In recent years a number of these novel agents have been assessed in preclinical and clinical trials. In this review, we introduce some of the key regulatory molecules that control the apoptotic pathways, extrinsic and intrinsic death receptors, discuss how defects in apoptotic pathways contribute to cancer, and list several agents being developed to target apoptosis.

Aprepitant in the Prevention of Vomiting Induced by Moderately and Highly Emetogenic Chemotherapy

  • Wang, Shi-Yong;Yang, Zhen-Jun;Zhang, Zhe;Zhang, Hui
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10045-10051
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    • 2015
  • Chemotherapy is a major therapeutic approach for malignant neoplasms; however, due to the most common adverse events of nausea and vomiting, scheduled chemotherapeutic programs may be impeded or even interrupted, which severely impairs the efficacy. Aprepitants, 5-HT3 antagonists and dexamethasone are primary drugs used to prevent chemotherapy-induced nausea and vomiting (CINV). These drugs have excellent efficacy for control of acute vomiting but are relatively ineffective for delayed vomiting. Aprepitant may remedy this deficiency. Substance P was discovered in the 1930s and its association with vomiting was confirmed in the 1950s. This was followed by a period of non-peptide neurokinin-1 (NK-1) receptor antagonist synthesis and investigation in preclinical studies and clinical trials (phases I, II and III). The FDA granted permission for the clinical chemotherapeutic use of aprepitant in 2003. At present, the combined use of aprepitant, 5-HT3 antagonists and dexamethasone satisfactorily controls vomiting but not nausea. Therefore, new therapeutic approaches and drugs are still needed.

The mTOR Signalling Pathway in Cancer and the Potential mTOR Inhibitory Activities of Natural Phytochemicals

  • Tan, Heng Kean;Moad, Ahmed Ismail Hassan;Tan, Mei Lan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6463-6475
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    • 2014
  • The mammalian target of rapamycin (mTOR) kinase plays an important role in regulating cell growth and cell cycle progression in response to cellular signals. It is a key regulator of cell proliferation and many upstream activators and downstream effectors of mTOR are known to be deregulated in various types of cancers. Since the mTOR signalling pathway is commonly activated in human cancers, many researchers are actively developing inhibitors that target key components in the pathway and some of these drugs are already on the market. Numerous preclinical investigations have also suggested that some herbs and natural phytochemicals, such as curcumin, resveratrol, timosaponin III, gallic acid, diosgenin, pomegranate, epigallocatechin gallate (EGCC), genistein and 3,3'-diindolylmethane inhibit the mTOR pathway either directly or indirectly. Some of these natural compounds are also in the clinical trial stage. In this review, the potential anti-cancer and chemopreventive activities and the current status of clinical trials of these phytochemicals are discussed.

Prevention of Lung Cancer: Future Perspective with Natural Compounds

  • Brandes, Johann C.;Amin, A.R.M. Ruhul;Khuri, Fadlo;Shin, Dong-Moon
    • Tuberculosis and Respiratory Diseases
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    • v.69 no.1
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    • pp.1-15
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    • 2010
  • Lung cancer remains the most common cause of cancer death in the United States and worldwide. About 80~90% of cases are smoking-related and smoking cessation programs are of great importance in reducing lung cancer risk. However, the lifetime risk for lung cancer remains elevated even in ex-smokers. Chemoprevention holds the promise to further reduce this risk and thus to decrease lung cancer incidence and mortality. Over the last decades, most chemoprevention trials for lung cancer have yielded negative outcomes. Population-based studies suggest that high intake of certain foods such as soy, red wine or green vegetables may be associated with decreased cancer risk. Because of these observations and their general safety, a plethora of natural compounds is currently being studied for the chemoprevention of cancer. In this review we discuss promising in vitro and in vivo data of novel natural compounds, their interference with molecular mechanisms responsible for lung cancer development and potential implications for their further preclinical and clinical investigation.

Concomitant EGFR Inhibitors Combined with Radiation for Treatment of Non-small Cell Lung Carcinoma

  • Zheng, De-Jie;Yu, Guo-Hua;Gao, Jian-Feng;Gu, Jun-Dong
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.8
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    • pp.4485-4494
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    • 2013
  • Epidermal growth factor receptor (EGFR) is considered to be one of the key driver genes in non-small cell lung cancer (NSCLC). Several clinical trials have shown great promise of EGFR tyrosine kinase inhibitors (TKIs) in the first-line treatment of NSCLC. Many advances have been made in the understanding of EGFR signal transduction network and the interaction between EGFR and tumor microenvironment in mediating cancer survival and development. The concomitant targeted therapy and radiation is a new strategy in the treatment of NSCLC. A number of preclinical studies have demonstrated synergistic anti-tumor activity in the combination of EGFR inhibitors and radiotherapy in vitro and in vivo. In the present review, we discuss the rationale of the combination of EGFR inhibitors and radiotherapy in the treatment of NSCLC.

Ginseng and Diabetes: The Evidences from In Vitro, Animal and Human Studies

  • Yuan, Hai-Dan;Kim, Jung-Tae;Kim, Sung-Hoon;Chung, Sung-Hyun
    • Journal of Ginseng Research
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    • v.36 no.1
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    • pp.27-39
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    • 2012
  • Panax ginseng exhibits pleiotropic beneficial effects on cardiovascular system, central nervous system, and immune system. In the last decade, numerous preclinical findings suggest ginseng as a promising therapeutic agent for diabetes prevention and treatment. The mechanism of ginseng and its active components is complex and is demonstrated to either modulate insulin production/secretion, glucose metabolism and uptake, or inflammatory pathway in both insulin-dependent and insulin-independent manners. However, human studies are remained obscure because of contradictory results. While more studies are warranted to further understand these contradictions, ginseng holds promise as a therapeutic agent for diabetes prevention and treatment. This review summarizes the evidences for the therapeutic potential of ginseng and ginsenosides from in vitro studies, animal studies and human clinical trials with a focus on diverse molecular targets including an AMP-activated protein kinase signaling pathway.

Trends of Innovative Clinical Drug Development using AMS (Accelerator Mass Spectrometry) and $^{14}C$-micro Tracer (가속질량분석기(Accelerator mass spectrometry, AMS)와 극미량 $^{14}C$-동위원소를 이용한 혁신적 임상시험개발동향)

  • Cho, Kyung Hee;Lee, Hee Joo;Choie, Hyung Sik;Lee, Kyoung Ryul;Dueker, Stephen R.;Shin, Young G.
    • YAKHAK HOEJI
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    • v.57 no.6
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    • pp.412-419
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    • 2013
  • Drug discovery and development processes are time consuming and costly endeavors. It has been reported that on average it takes 10 to 15 years and costs more than $ 1billion to bring a molecule from discovery to market. Compounds fail for various reasons but one of the significant reasons that accounts for failures in clinical trials is poor prediction/understanding of pharmacokinetics and drug metabolism in human. In an effort to improve the number of compounds that exhibit optimal absorption, distribution, metabolism, elimination (ADME), and pharmacokinetic properties in human, drug metabolism, pharmacokinetic scientists have been continually developing new technologies and compound screening strategies. Over the last few years, accelerator mass spectrometry (AMS) and its applications to preclinical/clinical pharmacokinetics and ADME studies have significantly increased, particularly for new chemical/biological entities that are difficult to support with conventional radiolabel studies. In this review, the application of AMS for micro-dosing, micro-tracer absolute bioavailability, mass balance and metabolite profiling studies will be discussed.

A Study on Amendment of Approval Specifications for Traditional Korean Medicines (한약제제 허가기준 개선방안 연구(I))

  • Han Byong-Hyon;Hwang Gwi-Seo
    • Journal of Society of Preventive Korean Medicine
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    • v.5 no.1
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    • pp.57-75
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    • 2001
  • This study was conducted to improve the current regulation guidelines for developing traditional Korean medicines with effectiveness and productivity, in order to cope with the upcoming ICH on specifications on oriental herbal drugs. Also, major purposes of this study are to motivate R&D and to pioneer foreign markets for domestic herbal drug companies. First, after examining concepts of traditional Korean medicines and comparing the numbers and differentiation of herbal drugs registered on Pharmacopeia among Korea, China, and Japan, the current new drug development requirements for traditional Korean medicines were reviewed in detail, followed by comparison of foreign regulation systems including USA, EU, China, and Japan. Second, empirical cases on failure of development for new traditional Korean medicines under the current regulation system in the domestic companies including Dong-A, Kwangdong, and Samchondang, were collected and analyzed. As a result, hanbangsaengyak, the new category for traditional Korean medicines was newly developed on the basis of scientification of data between saengyak and hanyak, from the perspectives of harmonization between oriental medicine and western medicine and of balance between food and drug, in terms of industrialization, publicity, modernization, and effectiveness of administration. In addition, the new regulation requirements for the new hanbangsaengyak preparations were discussed by establishing principles of reinforcing preclinical test and of simplifying clinical trials in Korea. Finally, the further researches to articulate the complete specifications for pre-clinical and clinical requirements for traditional Korean medicines were strongly suggested.

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