• Natural Product Sciences
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• v.8 no.1
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• pp.1-15
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• 2002

An International Cooperative Biodiversity Group (ICBG) program based at the University of Illinois at Chicago initiated its activities in 1998, with the following specific objectives: (a) inventory and conservation of of plants of Cuc Phuong National Park in Vietnam and of medicinal plants of Laos; (b) drug discovery (and development) based on plants of Vietnam and Laos; and (c) economic development of communities participating in the ICBG project both in Vietnam and Laos. Member-institutions and an industrial partner of this ICBG are bound by a Memorandum of Agreement that recognizes property and intellectual property rights, prior informed consent for access to genetic resources and to indigenous knowledge, the sharing of benefits that may arise from the drug discovery effort, and the provision of short-term and long-term benefits to host country institutions and communities. The drug discovery effort is targeted to the search for agents for therapies against malaria (antimalarial assay of plant extracts, using Plasmodium falciparum clones), AIDS (anti-HIV-l activity using HOG.R5 reporter cell line (through transactivation of the green fluorescent protein/GFP gene), cancer (screening of plant extracts in 6 human tumor cell lines - KB, Col-2, LU-l, LNCaP, HUVEC, hTert-RPEl), tuberculosis (screening of extracts in the microplate Alamar Blue assay against Mycobacterium tuberculosis $H_{37}Ra\;and\;H_{37}Rv),$ all performed at UIC, and CNS-related diseases (with special focus on Alzheimer's disease, pain and rheumatoid arthritis, and asthma), peformed at Glaxo Smith Kline (UK). Source plants were selected based on two approaches: biodiversity-based (plants of Cuc Phuong National Park) and ethnobotany-based (medicinal plants of Cuc Phuong National Park in Vietnam and medicinal plants of Laos). At mc, as of July, 2001, active leads had been identified in the anti-HIV, anticancer, antimalarial, and anti- TB assay, after the screening of more than 800 extracts. At least 25 biologically active compounds have been isolated, 13 of which are new with anti-HIV activity, and 3 also new with antimalarial activity. At GSK of 21 plant samples with a history of use to treat CNS-related diseases tested to date, a number showed activity against one or more of the CNS assay targets used, but no new compounds have been isolated. The results of the drug discovery effort to date indicate that tropical plant diversity of Vietnam and Laos unquestionably harbors biologically active chemical entities, which, through further research, may eventually yield candidates for drug development. Although the substantial monetary benefit of the drug discovery process (royalties) is a long way off, the UIC ICBG program provides direct and real-term benefits to host country institutions and communities.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.1
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• pp.1-24
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• 2003

This study was done to compile 104 experimental theses which are related to the antitumor and immuno-activating therapies between February 1990 through February 2002. Master's and doctoral theses were dassified by schools, degrees, materials, effects, experimental methods of antitumor and immunoactivity, and results. The following results were obtained from this study : 1. Classifying the theses by the school, 34.6% were presented by Daejeon University, 29.8% by Kyung-hee University and 11.5% by Won-kwang University. Of all theses, 51.0% were aimed for the doctoral degree and 43.3% were for the master's degree. All of three universities have their own cancer centers. 2. Classifying the theses by herb materials, complex prescription accounted for 60.3%, single herb accounted for 24.8% and herbal acupuncture accounted for 14.2%. Considering the key principles of the traditional medicine, complex prescription was much more thoroughly studied than single herb prescription. The results showed that the complex prescription had both antitumor activity and immuno-activating activity, which might reflects on multi-activation mechanisms by complex components. 3. Classifying the theses by the efficacy of herbs examined, in single herb, invigorating spleen and supplementing was 35.5%, expelling toxin and cooling was 29.0%, activating blood flow and removing blood stasis was 12.9%. In herbal acupuncture, invigorating spleen and supplementing was 52.9%, expelling toxin and cooling was 29.4%. In complex prescription, pathogen-free status was 41.9%, strengthening healthy qi to eliminate pathogen was 35.5%, strengthening healthy qi was 22.6%. It is presumed that the antitumor and immunoactivating therapy based on syndrome differentiation is the best way to develop oriental oncology. 4. Classifying the theses by antitumor experiments, cytotoxic effect was 48.1 %, survival time was 48.1 % and change of tumor size was 42.3%. Survival rate was not necessarily correlated with cytotoxicity. These data reflect the characteristic, wholistic nature of the oriental medicine which is based on BRM (biological response modifier). 5. Classifying the theses by immunoactivating experiments, hemolysin titer was 51.0%, hemagglutinin titer was 46.2% and NK cell's activity was 44.2%. In the future studies, an effort to elucidate specific molecular and cellular mechanisms of cytokine production in the body would be crucial. 6. Classifying the theses according to the data in terms of antitumor activity, 50% was evaluated good, 24.0% was excellent, and 15.5% have no effect. In an evaluation of immuno-activating activity, 35.9% was excellent and 18.0% showed a little effect. The index point, as described here, may helps to use experimental data for clinical trials. Changes in index points by varying dosage implicate the importance of oriental medical theory for prescription. 7. In 167 materials, IIP (immunoactivating index point, mean : 3.12±0.07) was significantly higher than AIP(antitumor index point, mean : 2.83±0.07). These data demonstrate that the effect of herb medicine on tumor activity depends more on immunoactivating activity than antitumor activity. This further implies that the development of herbal antitumor drugs must be preceded by the mechanistic understanding of immunoactivating effect. 8. After medline-searching tumor and herb-related articles from NCBI web site, we conclude that most of the studies are primarily focused on biomolecular mechanisms and/or pathways. Henceforth, we need to define the biomolecular mechanisms and/or pathways affected by herbs or complicated prescriptions. 9. Therefore, the most important point of oriental medical oncology is to conned between experimental results and clinical trials. For the public application of herbal therapy to cancer, it is critical to present the data to mass media. 10. To develop the relationship of experimental results and clinical trials, university's cancer clinic must have a long-range plan related to the university laboratories and, at the same time, a regular consortium for this relationship is imperative. 11. After all these efforts, a new type herbal medicine for cancer therapy which is to take care of the long-term administering and safety problem must be developed. Then, it would be expected that anti-tumor herbal acupuncture can improve clinical symptoms and quality of life (QOL) for cancer patients. 12. Finally, oriental medical cancer center must be constructed in NCC (National Cancer Center) or government agency for the development of oriental medical oncology which has international competitive power.

• Journal of Mushroom
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• v.11 no.1
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• pp.46-51
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• 2013

Sparassis crispa is a medicinal mushroom, which has been reported to have anti-cancer effect. In this study, we designed to investigate the effects of Sparassis crispa extracts on the production of nitric oxide (NO) in LPS-stimulated RAW264.7 cells. The pre-treatment of the extracts prior to add LPS in RAW264.7 cells suppressed NO production and iNOS expression at protein and mRNA levels. The phosphorylation of $I{\kappa}B{\alpha}$ was inhibited by the extracts, which was induced through suppressing the activation of $NF-{\kappa}B$. Sparassis crispa extracts showed the effect on the down-regulation of STAT-1 activation in a dose-dependent manner. In LPS-stimulated RAW264.7 cells, $NF-{\kappa}B$ was translocated into the nucleus, while the treatment of Sparassis crispa extracts induced to sequestered $NF-{\kappa}B$ in the cytosol. These experimental results determined that Sparassis crispa extracts play a inhibitory role in inflammatory reactions via regulating NO production, which suggests potential as a component of inflammatory drugs.

• The Journal of Internal Korean Medicine
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• v.21 no.3
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• pp.443-452
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• 2000

Objective : This study was designed to evaluate the synergistic effect on cytotoxicity of combination with adriamycin and Palginhonhapwhajucwhan, a traditional prescription for cancer treatment in oriental medicine, in Chang, HL-60, Hep-3B and Alexander cells. Methods : We observed cell viability in Chang, HL-60, Hep-3B, and Alexander cells by crystal violet staining. Those cells were treated with various concentrations of adriamycin alone, Palginhonhapwhajucwhan alone and combination of two medications for 10 hr. On condition of $0.5{\mu}l/ml$ adriamycin alone, $15.6{\mu}l/ml$ Paljintanghapwhajucwhan alone and combination of two medications, at first, we observed colony forming of Chang and HL-60 cells. Second, we observed DNA fragmentation by agarose electrophoresis in Chang, HL-60, Hep-38 and Alexander cells. Third, we measured the catalytic activation of caspase-1, 2, 3, 6, 8, and 9 protease in Chang cells and caspase-3 protease in Chang, HL-60, Hep-3B and Alexander cells by using fluorogenic substrate. Finally, we isolated mRNA of Fas in Chang, HL-60, Hep-38 and Alexander cells and observed that Fas gene was amplified by RT-PCR Results : 1. The combination of adriamycin and Palginhonhapwhajucwhan synergistically augmented the cytotoxicity of Chang and HL-60 cells whereas did not in Hep-38 and Alexander cells. 2. Cotreatment of two drugs also markedly inhibited the colony forming ability both in Chang and HL-60 cells. 3. The cytotoxicity of these medicatons was revealed as apoptosis characterized by high molecular wight DNA fragmentaton. 4. The apoptotic cytotoxicity was mediated by activation of caspase-3 protease in Chang cells. 5. Synergistic increase in apoptotic cytotoxicity by combination of two medications was dependent on the expression of Fas in cancer cells. Conclusions : Combination of adriamycin and Palginhonhapwhajucwhan significantly augmented apoptotic cytotoxicity of Fas-positive cells such as Chang and HL-60 cells via acticaton of apoptosis signaling pathway.

• Journal of Life Science
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• v.31 no.2
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• pp.223-228
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• 2021

Cyclophosphamide (CP) is widely used in cancer and lymphoma treatments and as an immunosuppressant drug. CP is a DNA alkylating agent that metabolizes into 4-hydrocyclophosphamide (4H-CYP) and aldophosphamide in hepatocytes. However, its metabolites cause DNA synthesis disorder, leading to apoptosis and toxic side effects. The development of technology to minimize this side effect is essential to improve CP's clinical application. Various bioactive compounds have been reported to have anti-cancer and antioxidant functions and preventive or therapeutic roles in metabolic diseases. Many researchers have attempted to minimize the side effects and improve the efficacy of these drugs together with the use of bioactive compounds. Ulmus macrocarpa Hance has been used for the treatment of edema, mastitis, stomach pain, tumors, cystitis, and other inflammatory diseases. The aim of this study was to investigate at the histological level the protective function of U. macrocarpa Hance against CP's side effects and any potential toxic effect of U. macrocarpa Hance in the liver and kidney. Water extracts of U. macrocarpa Hance reduced CP-induced toxicity and did not induce any histological damage in the liver and kidney. Therefore, U. macrocarpa Hance would be applicable in the pharmaceutical industry.

• Journal of Hospice and Palliative Care
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• v.20 no.3
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• pp.177-187
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• 2017

Purpose: From August 2017, hospice-palliative care (HPC) will be provided to patients with acquired immunodeficiency syndrome (AIDS), chronic obstructive pulmonary disease (COPD), and liver cirrhosis in Korea. To contribute to building a non-cancer (NC) hospice-palliative care model, NC specialists were interviewed regarding the goals, details, and provision methods of the model. Methods: Four physicians specializing in HPC of cancer patients formulated a semi-structured interview with questions extracted from literature review of 85 articles on NC HPC. Eleven NC disease specialists were interviewed, and their answers were analyzed according to the qualitative content analysis process. Results: The interviewees said as follows: It is difficult to define end-stage NC patients. HPC for cancer patients and that for NC patients share similar goals and content. However, emphasis should be placed on alleviating other physical symptoms and emotional care rather than pain control. Timing of the care provision should be when patients are diagnosed as "end stage". Special issues should be considered for each NC disease (e.g., use of anti-retroviral drugs for AIDS patients, oxygen supply for COPD patients suffering from dyspnea, liver transplantation for patients with liver cirrhosis) and education should be provided to healthcare professionals. NC patients tend to negatively perceive HPC, and the government's financial assistance is insufficient. Conclusion: It is necessary to define end-stage NC patients through in-depth discussion to minimize issues that will likely accompany the expansion of care recipients. This requires cooperation between medical staff caring for NC patients and HPC givers for cancer patients.

• 한국생물공학회:학술대회논문집
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• 2001.11a
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• pp.867-870
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• 2001

All-trans-retinoic acid (RA) plays essential roles in the regulation of differentiation and proliferation. It has been proved that RA is effective in the treatments of epithelial and hematologic malignancies. However, in spite of its pronounced effects, the clinical applications of RA are limited due to the retinoid acute resistance. Although RA induces complete remission in a high proportion of the patients of acute promyelocytic leukemia (APL), the cancer was relapsed in many patients after a brief remission in spite of a continued RA treatment. Patients who relapsed from remission that was initially induced by RA had clinically resistant to further RA treatment. That is, specific cytochrome P450 enzymes in the liver were induced by the continuous oral administration of RA, thereby accelerating the metabolism of RA. To overcome this problem, biodegradable microspheres were proposed by us, previously. And, several microsphere formulations for RA delivery have been prepared and studied on their effectiveness. Recently, poly(D,L-lactide) (PDLLA) microsphere formulation was optimized, And, from the animal studies by using a mouse and a rat, it have appeared to be effective on both the inhibition of tumor growth and chemoprevention of a carcinogenesis. In this study, subacute toxicities of the PDLLA microsphere formulation have been investigated as a preclinical test. For the test, the microspheres was injected subcutaneously into the back site of rats, and body weight change, clinical signs, hematological changes, blood biochemistry were evaluated. As a result, severe toxicities such as mortality were observed at the dose of 100mg RA/kg, and toxicities were not observed at the dose of 50mg RA/kg, which is the effective dose against carcinogenesis. Bone fracture, observed at several rats, might be inhibited by treating them with anti-inflammatory drugs.

• Microbiology and Biotechnology Letters
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• v.39 no.2
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• pp.104-110
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• 2011

Actinomycetes, Gram positive soil bacteria, are valuable microorganisms which produce useful secondary metabolites including antibiotics, antiparasitic substances, anti-cancer drugs, and immunosuppressants. Although a major family of actinomycetes, known as streptomycetes, has been intensively investigated at the molecular level for several decades, a potentially valuable and only recently isolated non-streptomycetes rare actinomycetes (NSRA) family has been poorly characterized due to lack of proper genetic manipulation systems. Here we report that a PCR-based genome screening strategy was performed with approximately 180 independently isolated actinomycetes strains to isolate potentially valuable NSRA strains. Thanks to this simple PCR-based genome screening strategy we were able to identify only seven NSRA strains, followed by 16S rRNA sequencing for confirmation. Through further bioassays, one potentially valuable NSRA strain (tentatively named Nocardiopsis species MMBL010) was identified which possessed both antifungal and antibacterial activities, along with the presence of polyketide synthase and non-ribosomal peptide synthase genes. Moreover, Nocardiopsis species MMBL010, which was intrinsically recalcitrant to genetic manipulation, was successfully transformed via E. coli-driven conjugation. These results suggest that PCR-based genome screening, followed by the establishment of an E. coli-driven conjugation system, is an efficient strategy to maximize potentially valuable compounds and their biosynthetic genes from NSRA strains isolated from various environments.

• The Korean Society of Law and Medicine
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• v.13 no.2
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• pp.11-38
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• 2012

The Supreme Court stand in the position in specific lawsuit that it doesn't allow the discretionary not covered service, but recently in revocation suit of fine disposal that is imposed on medical fee of leukemia patient, it altered the existing adjudgement and admitted the discretionary not covered service exceptionally. It put forward the allowable condition roughly in that case. According as this alteration, it has become more important to embody the allowance conditions of exceptions. The Supreme Court presented three things, which are procedural condition, medical condition and subscriber's agreement. Concerning procedural condition, several present conciliation procedures are as follows: medical care benefit arret request, relative value conciliation etc, prior request on anti-cancer drug among chemicals which exceed acceptance criteria, request of non benefit object on common drugs. To be granted the existence of those system, there should be no obstacle to use that. Even if it were so, we should take circumstances into consideration; individual situation is unescapable concerning substance and urgency of the discretionary not covered service, process of the procedure, time required etc. Regarding medical condition, safety and effectiveness will be verified through evaluation procedures of new medical skill. About the necessity, the Supreme Court made clear through a sentence that it allow the discretionary not covered service, in case that needs to treat a patient out of the standard of medical benefit. Strict interpretation is right and it answer the purpose of the sentence that the supreme court permit the discretionary not covered service, exceptionally. We need to differentiate medical necessity and medical validity. Subscriber's agreement should holds true if it entails full explanation, and if it is preliminary, explicit and individual. On this account, it should be difficult to admit that someone agree effectively when he call for the affirmation that he is recipient of medical care. Reasonable expense needs to be a part of review whether the agreement is valid. Meanwhile If we adjust system of medical expense and eventually reorganize a fee for consultation payment system (Fee-for-service controlled by item to DRG (Diagnosis Related Groups)), controversial area of the discretionary not covered service will be decreased and that will guarantee the discretion of the doctor.

• Applied Chemistry for Engineering
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• v.29 no.2
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• pp.138-146
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• 2018

Photodynamic therapy (PDT) is a great potential approach for the localized tumor removal with fewer metastatic potentials and side effects in treating the disease. In the treatment process, a photosensitizer (PS) that absorbs a light energy to generate reactive oxygen is essential. In general, a visible light is used as a light source of PDT, so that side effects from the light source are inevitable. For this reason, upconversion nanoparticles (UCNPs) using near-infrared (NIR) as an excitation source are attracting attention in the field of disease diagnosis and treatment. UCNPs have the low cytotoxicity and phototoxicity, and also advantages such as deep tissue penetration and low background autofluorescence. For PDT, UCNPs should be combined with a PS which absorbs the light energy from UCNPs and transfers it to the surrounding oxygen to produce reactive oxygen. In addition, the therapeutic efficacy can be improved by modifying nanoparticle surfaces, adding anti-cancer drugs, or combining with photothermal therapy (PTT). In this review, we summarize the recent research to improve the efficiency of PDT using UCNPs.