• Title/Summary/Keyword: Drug response

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The role of necroptosis in the treatment of diseases

  • Cho, Young Sik
    • BMB Reports
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    • v.51 no.5
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    • pp.219-224
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    • 2018
  • Necroptosis is an emerging form of programmed cell death occurring via active and well-regulated necrosis, distinct from apoptosis morphologically, and biochemically. Necroptosis is mainly unmasked when apoptosis is compromised in response to tumor necrosis factor alpha. Unlike apoptotic cells, which are cleared by macrophages or neighboring cells, necrotic cells release danger signals, triggering inflammation, and exacerbating tissue damage. Evidence increasingly suggests that programmed necrosis is not only associated with pathophysiology of disease, but also induces innate immune response to viral infection. Therefore, necroptotic cell death plays both physiological and pathological roles. Physiologically, necroptosis induce an innate immune response as well as premature assembly of viral particles in cells infected with virus that abrogates host apoptotic machinery. On the other hand, necroptosis per se is detrimental, causing various diseases such as sepsis, neurodegenerative diseases and ischemic reperfusion injury. This review discusses the signaling pathways leading to necroptosis, associated necroptotic proteins with target-specific inhibitors and diseases involved. Several studies currently focus on protective approaches to inhibiting necroptotic cell death. In cancer biology, however, anticancer drug resistance severely hampers the efficacy of chemotherapy based on apoptosis. Pharmacological switch of cell death finds therapeutic application in drug- resistant cancers. Therefore, the possible clinical role of necroptosis in cancer control will be discussed in brief.

The study about Sasang Constitution diagnosis and research trends in the case reports (증례논문에 나타난 사상체질진단의 특징 및 연구동향에 대한 연구)

  • Ban, Duk-Jin;Lee, Seung-Yun;Park, Seong-Sik
    • Journal of Sasang Constitutional Medicine
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    • v.21 no.2
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    • pp.107-114
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    • 2009
  • 1. Objectives : We analyzed the case reports published by the journal of Sasang Constitutional Medicine, to study Sasang Constitution diagnosis and characteristic of clinical practice. 2. Methods : It has been examined 138 case reports of Sasang Constitution society published from 1994 to 2008. We analyzed. patient's number, publication year, distribution of Sasang Constitution, title's characteristics and bases of constitution diagnosis. 3. Results and conclusions : 1) In the analysis of patient's number, 1 case report was almost part of the case reports, and the case reports ware many published after 2001. 2) In the analysis distribution of Sasang Constitution, Soyangin was the most Sasang Constitution, and Tae-umin was the next one and Soeumin, Taeyangin followed them. 3) In the analysis of the journal's title, Sasang Constitution, disease and symptom of Sasang Constitution were more important than prescription recently. 4) In the analysis of the journal's purpose, unique disease and response of treatment were almost part of the case reports. 5) In the analysis of diagnosis bases, subjective bases were more important than objective bases and Sasang Constitutional drug response. therefore we should do researches in objective bases and drug response in the future.

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Microscopic Image-based Cancer Cell Viability-related Phenotype Extraction (현미경 영상 기반 암세포 생존력 관련 표현형 추출)

  • Misun Kang
    • Journal of Biomedical Engineering Research
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    • v.44 no.3
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    • pp.176-181
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    • 2023
  • During cancer treatment, the patient's response to drugs appears differently at the cellular level. In this paper, an image-based cell phenotypic feature quantification and key feature selection method are presented to predict the response of patient-derived cancer cells to a specific drug. In order to analyze the viability characteristics of cancer cells, high-definition microscope images in which cell nuclei are fluorescently stained are used, and individual-level cell analysis is performed. To this end, first, image stitching is performed for analysis of the same environment in units of the well plates, and uneven brightness due to the effects of illumination is adjusted based on the histogram. In order to automatically segment only the cell nucleus region, which is the region of interest, from the improved image, a superpixel-based segmentation technique is applied using the fluorescence expression level and morphological information. After extracting 242 types of features from the image through the segmented cell region information, only the features related to cell viability are selected through the ReliefF algorithm. The proposed method can be applied to cell image-based phenotypic screening to determine a patient's response to a drug.

Appropriate Block Level in Neurolytic Lumbar Sympathetic Ganglion Block (신경파괴적 요부교감신경절 차단의 적정 부위)

  • Kim, Hee-Jung;Lee, Cheol-Oh;Shin, Yang-Sik;Lee, Youn-Woo
    • The Korean Journal of Pain
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    • v.14 no.2
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    • pp.199-206
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    • 2001
  • Background: The lumbar sympathetic ganglia are variable in both position and numbers. The aim of this study was to detect the appropriate lumbar vertebral level where the lumbar sympathetic ganglia primarily aggregate. Methods: Forty patients comprising of hyperhidrosis (26 cases), complex regional pain syndrome (10 cases), peripheral artery occlusion disease (3 cases) and postherpetic neuralgia (1 case) underwent lumbar sympathetic block. We randomly selected one of two (L2 or L3) levels and the L4 level. The position of the needle tip and distribution of dye was verified by injection of a mixture of radio-opaque dye (1.5 ml) and 4% lidocaine (1.5 ml) and subsequently confirmed by L-spine anteroposterior and a lateral view X-ray. We considered the response positive when the skin temperature increased more than $1^{\circ}C$ in 5 min. Results: In general, the positive response ratio was greater when the needle tip located at the L2 or L4 level vice L3 and when the drug was distributed on the lower half of the L4 body and in the L4/5 intervertebral disc space. In a right side block, the positive response ratio was greater when the drug was distributed on the lower half of the L4 body and in the L4/5 intervertebral disc space, although in a left side block there was no significant difference seen between the levels. The complications of the neurolytic block were alcohol neuritis (7.5%) and hypoesthesia (5%) on the L1 or L2 dermatome. Conclusions: The best effect with least chance of complication may be induced by spreading the drug on the lower half of the L4 body and/or into the L4/5 intervertebral disc space by placing the needle tip on the L4 body.

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Application of Lobaplatin in Trans-catheter Arterial Chemoembolization for Primary Hepatic Carcinoma

  • Wang, Nan;Lv, Yin-Zhang;Xu, An-Hui;Huang, Yan-Rong;Peng, Ling;Li, Jia-Rui
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.647-650
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    • 2014
  • Objective: To explore the efficiency of single application of lobaplatin in tran-scatheter arterial chemoembolization (TACE) for patients with a primary hepatic carcinoma who were unable or unwilling to undergo surgery. Methods: 173 patients with primary hepatic carcinoma diagnosed by imaging or pathology were randomly divided into experimental and control groups and respectively treated with lobaplatin and pirarubicin hydrochloride as chemotherapeutic drugs for TACE. The amount of iodipin was regulated according to the tumor number and size, and then gelatin sponge or polyvinyl alcohol particles were applied for embolisms. The efficiency of treatment in the two groups was compared with reference to survival time and therapeutic response. Results: The experimental group (single lobaplatin as chemotherapy drug) was superior to control group (single pirarubicin hydrochloride as chemotherapy drug) in the aspects of survival time and therapeutic response, with statistical significance. Conclusions: Single lobaplatin can be as a chemotherapy drug in TACE and has better efficiency in the aspects of mean survival time and therapeutic response, deserving to be popularized in the clinic.

Silibilin-Induces Apoptosis in Breast Cancer Cells by Modulating p53, p21, Bak and Bcl-xl Pathways

  • Pirouzpanah, Mohammad Bagher;Sabzichi, Mehdi;Pirouzpanah, Saeed;Chavoshi, Hadi;Samadi, Nasser
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.2087-2092
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    • 2015
  • Nowadays herbal-derived medicines are attracting attention as new sources of drugs with few side effects. Silibinin is a flavonoid compound with chemotheraputic effects on different cancers such as examples in the prostate, lung, colon and breast. In the present study, the cytotoxic effects of silibinin on MCF7 breast cancer cells were investigated. Apoptosis was determined by flow cytometry and the impact of silibinin on the expression of pivotal genes including Bak, P53, P21, BRCA1, BCL-X1 and ATM was analyzed. Treatment for 24h had a significant dose-dependent inhibitory effect on cell growth (p<0.05) with dose- and time- dependent induction of apoptosis (p<0.05). In addition, there were significant increases in BRCA1, ATM, Bak and Bcl-XL gene expression at the mRNA level with different concentrations of silibinin for 24 or 48 h (p<0.05). Taken together, the results suggest that silibinin inhibits the proliferation and induces apoptosis of MCF-7 cells by down-regulating Bak, P53, P21, BRCA1, BCL-Xl and thus may be considered as an effective adjuvant drug to produce a better chemopreventive response for the cancer therapy.

Neuroimaging in Nuclear Medicine: Drug Addicted Brain (약물 중독 환자의 뇌신경계 핵의학 영상)

  • Chung, Yong-An;Kim, Dae-Jin
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.1
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    • pp.1-8
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    • 2006
  • Addiction to illicit drugs is one of today's most important social issues. Most addictive drugs lead to irreversible parenchymal changes in the human brain. Neuroimaging data bring to light the pharmacodynamics and pharmacokinetics of the abused drugs, and demonstrate that addiction is a disease of the brain. Continuous researches better illustrate the neurochemical alterations in brain function, and attempt to discover the links to consequent behavioral changes. Newer hypotheses and theories follow the numerous results, and more rational methods of approaching therapy are being developed. Substance abuse is on the rise in Korea, and social interest in the matter as well. On the other hand, diagnosis and treatment of drug addiction is still very difficult, because how the abused substance acts in the brain, or how it leads to behavioral problems is not widely known. Therefore, understanding the mechanism of drug addiction can improve the process of diagnosing addict patients, planning therapy, and predicting the prognosis. Neuroimaging approaches by nuclear medicine methods are expected to objectively judge behavioral and neurochemical changes, and response to treatment. In audition, as genes associated with addictive behavior are discovered, functional nuclear medicine images will aid in the assessment of individuals. Reviewing published literature on neuroimaging regarding nuclear medicine is expected to be of assistance to the management of drug addict patients. What's more, means of applying nuclear medicine to the care of drug addict patients should be investigated further.

Arsenic Trioxide Promotes Paclitaxel Cytotoxicity in Resistant Breast Cancer Cells

  • Bakhshaiesh, Tayebeh Oghabi;Armat, Marzie;Shanehbandi, Dariush;Sharifi, Simin;Baradaran, Behzad;Hejazi, Mohammad Saeed;Samadi, Nasser
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.13
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    • pp.5191-5197
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    • 2015
  • A partial response or resistance to chemotherapeutic agents is considered as a main obstacle in treatment of patients with cancer, including breast cancer. Refining taxane-based treatment procedures using adjuvant or combination treatment is a novel strategy to increase the efficiency of chemotherapy. PPM1D is a molecule activated by reactive oxygen species. whose expression is reported to modulate the recruitment of DNA repair molecules. In this study we examined the impact of arsenic trioxide on efficacy of paclitaxel-induced apoptosis in paclitaxel-resistant MCF-7 cells. We also investigated the expression of PPM1D and TP53 genes in response to this combination treatment. Resistant cells were developed from the parent MCF-7 cell line by applying increasing concentrations of paclitaxel. MTT assays were applied to determine the rate of cell survival. DAPI staining using fluorescent microscopy was employed to study apoptotic bodies. Real-time RT-PCR analysis was also applied to determine PPM1D mRNA levels. Our results revealed that combination of arsenic trioxide and paclitaxel elevates the efficacy of the latter in induction of apoptosis in MCF-7/PAC resistant cells. Applying arsenic trioxide also caused significant decreases in PPM1D mRNA levels (p<0.05). Our findings suggest that arsenic trioxide increases paclitaxel-induced apoptosis by down regulation of PPM1D expression. PPM1D dependent signaling can be considered as a novel target to improve the efficacy of chemotherapeutic agents in resistant breast cancer cells.

Abuse Liability Assessment of l-Deprenyl by Testing Methamphetamine-like Discriminative Effects (메탐페타민 유사 분별능 시험을 통한 l-디프레닐의 약물남용가능성 평가)

  • Lee, Sun-Hee;Kim, Pu-Young
    • YAKHAK HOEJI
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    • v.42 no.1
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    • pp.101-107
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    • 1998
  • The antiparkinsonian agent l-deprenyl, a selective monoamine oxidase (MAO)-B inhibitor, is metabolized in part to l-methamphetamine and l-amphetamine. l< /I>-Deprenyl was evaluated for amphetamine and methamphetamine-like discriminative stimulus effects in rats and its mechanism of action was investigated. Rats were trained under a 5-response, fixed ratio schedule of stimulus-shock termination or a 10-response. Fixed-ratio schedule of food-presentation which discriminate between d-amphetamine (1mg/kg, i.p.) and saline or d-methamphetamine (1mg/kg, i.p.) and saline in a two-lever, operant conditioning procedure. Full generalization was obtained to d-amphetamine (1~3mg/kg). d-methamphetamine (1~3mg/kg) and l-deprenyl (17~30mg/kg) under both the food presentation and stimulus shock termination schedule. l-Deprenyl has dose-dependent amphetamine-and methamphetamine-like discriminative stimulus properties in rats only at doses of 17 and 30mg/kg. Reversible MAO-B inhibitor, RO 16-6491 didn`t show any amphetamine-like discriminative properties. Aromatic amino acid decarboxylase inhibitor, NSD 1015 decreased % responding of l-deprenyl in the methamphetamine-trained rats under the stimulus-shock termination schedule. SKF-525A produced partial inhibition of methamphetamine-like discriminative effects of l-deprenyl under the food presentation schedule. These results suggest that l-deprenyl has no abuse liability at the therapeutic range but there needs some caution at high doses and furthermore, drug discrimination studies under the food presentation and shock termination schedule are useful for the assessment of abuse liability of psychostimulants.

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Effects of Olaquindox and Cyadox on Immunity of Piglets Orally Inoculated with Escherichia coli

  • Ding, Mingxing;Yuan, Zonghui;Wang, Yulian;Zhu, Huiling;Fan, Shengxian
    • Asian-Australasian Journal of Animal Sciences
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    • v.18 no.9
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    • pp.1320-1325
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    • 2005
  • A 2${\times}$3 factorial arrangement of treatments was used to determine the effects of olaquindox and cyadox on immune response of Landrace${\times}$Large-White geld piglets that had been orally given 10$^{10}$ CFU of Escherichia coli (E. coli, O$_{139}$:K$_{88}$). Factors included (1) E. coli inoculation or control, and (2) no antimicrobials, 100 mg/kg olaquindox and 100 mg/kg cyadox in the basal diet respectively. E. coli inoculums were orally administered 7 days after the diets were supplemented with olaquindox and cyadox. The effects of the two antimicrobials were assessed in terms of: (1) average daily gain (ADG), (2) systemic immune response (the number of white blood cells and lymphocytes, leukocyte bactericidal capacity, lymphocyte proliferation response to PHA, immunoglobulin concentrations, and total serous hemolytic complement activity), and (3) intestinal mucosal immunity including the number of intraepithelial lymphocytes (IELs) and immunoglobulin A secreting cells (ASCs) in the intestinal lamina propria. E. coli inoculation reduced ADG (p<0.05) during the period of d 0 to d 14 after the challenge while the antimicrobial supplementations improved ADG (p<0.01) during the experiment. ADG in cyadox-supplemented pigs was higher (p<0.05) than that in olaquindox-supplemented pigs. The antimicrobials decreased IEL and ASC counts in the jejunum and ileum (p<0.01) while E. coli inoculation caused them to increase (p<0.01). Jejunal ASCs in the cyadox-supplemented pigs were lower (p<0.05) than those in the olaquindox-supplemented. E. coli elicited increase (p<0.05) in white blood cell counts, leukocyte bactericidal capacity, lymphocyte proliferation rate, serous IgA concentrations, and serous hemolytic complement activity. The antimicrobials decreased the measured systemic immune parameters, but not significantly (p>0.05). The data suggest that olaquindox and cyadox suppress E. coli-induced immune activation, especially intestinal mucosal immune activation, which may be involved in the observed growth promotion.