• Title/Summary/Keyword: Targeted therapy

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Analysis of CEA Expression and EGFR Mutation Status in Non-small Cell Lung Cancers

  • Yang, Zhong-Ming;Ding, Xian-Ping;Pen, Lei;Mei, Lin;Liu, Ting
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3451-3455
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    • 2014
  • Background: The serum carcinoembryonic antigen (CEA) level can reflect tumor growth, recurrence and metastasis. It has been reported that epidermal growth factor receptor (EGFR) mutations in exons 19 and 21may have an important relationship with tumor cell sensitivity to EGFR-TKI therapy. In this study, we investigated the clinical value of EGFR mutations and serum CEA in patients with non-small cell lung cancer (NSCLC). Materials and Methods: The presence of mutations in EGFR exons 19 and 21 in the tissue samples of 315 patients with NSCLC was detected with real-time fluorescent PCR technology, while the serum CEA level in cases who had not yet undergone surgery, radiotherapy, chemotherapy and targeted therapy were assessed by electrochemical luminescence. Results: The mutation rates in EGFR exons 19 and 21 were 23.2% and 14.9%, respectively, with the two combined in 3.81%. Measured prior to the start of surgery, radiotherapy, chemotherapy and targeted treatment, serum CEA levels were abnormally high in 54.3% of the patients. In those with a serum CEA level <5 ng/mL, the EGFR mutation rate was 18.8%, while with 5~19 ng/mL and ${\geq}20ng/mL$, the rates were 36.4% and 62.5%. In addition, in the cohort of patients with the CEA level being 20~49 ng/mL, the EGFR mutation rate was 85.7%, while in those with the CEA level ${\geq}50ng/mL$, the EGFR mutation rate was only 20.0%, approximately the same as in cases with the CEA level<5 ng/mL. Conclusions: There is a positive correlation between serum CEA expression level and EGFR mutation status in NSCLC patients, namely the EGFR mutation-positive rate increases as the serum CEA expression level rises within a certain range (${\geq}20ng/mL$, especially 20~49 ng/mL). If patient samples are not suitable for EGFR mutation testing, or cannot be obtained at all, testing serum CEA levels might be a simple and easy screening method. Hence, for the NSCLC patients with high serum CEA level (${\geq}20ng/mL$, especially 20~49 ng/mL), it is worthy of attempting EGFR-TKI treatment, which may achieve better clinical efficacy and quality of life.

Trastuzumab in a Patient with Metastatic Salivary Duct Carcinoma : A Case Report (트라스투주맙 치료에 반응을 보인 HER2/neu 양성 전이성 타액관 암종 1예)

  • Kong, Bong Han;Lee, Jieun;Choi, Sang-Su;Park, Jinhee;Kim, Yeon Shil;Kim, Min-Sik;Lee, Youn-Soo;Lee, Ji-Yeon;Hong, Sook Hee;Kang, Jin Hyoung
    • Korean Journal of Head & Neck Oncology
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    • v.30 no.2
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    • pp.90-94
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    • 2014
  • Salivary duct carcinoma(SDC) is rare malignancy, accounting for approximately 1-3% of all malignant salivary gland tumors. Systemic chemotherapy has been used for stage IV SDC, but there is no consensus on the standard treatment. SDC is histologically similar to ductal carcinoma of breast and often overexpress HER2/neu, hence HER2/neu targeted therapy could be one of treatment options. A 75-year-old Arabian man was diagnosed as SDC of right parotid gland with extensive metastases. He received oral 5-FU as palliative chemotherapy, but he was intolerable to oral chemotherapy due to severe oral mucositis. Considering immunohistochemical stain of tumor tissue showing strong positive for HER2/neu, we decided to administer an anti-HER2/neu antibody, trastuzumab. Follow-up CT scans before the third dose of trastuzumab demonstrated remarkable regression of multiple metastases as well as primary tumor. This case suggests that HER2/neu targeted therapy may be a potential therapeutic option for the SDC patient with overexpression of HER2/neu.

Interplay between the Gut Microbiome and Metabolism in Ulcerative Colitis Mice Treated with the Dietary Ingredient Phloretin

  • Ren, Jie;Li, Puze;Yan, Dong;Li, Min;Qi, Jinsong;Wang, Mingyong;Zhong, Genshen;Wu, Minna
    • Journal of Microbiology and Biotechnology
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    • v.31 no.10
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    • pp.1409-1419
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    • 2021
  • A growing number of healthy dietary ingredients in fruits and vegetables have been shown to exhibit diverse biological activities. Phloretin, a dihydrochalcone flavonoid that is abundant in apples and pears, has anti-inflammatory effects on ulcerative colitis (UC) mice. The gut microbiota and metabolism are closely related to each other due to the existence of the food-gut axis in the human colon. To investigate the interplay of faecal metabolites and the microbiota in UC mice after phloretin treatment, phloretin (60 mg/kg) was administered by gavage to ameliorate dextran sulfate sodium (DSS)-induced UC in mice. Gut microbes and faecal metabolite profiles were detected by high-throughput sequencing and liquid chromatography mass spectrometry (LC-MS) analysis, respectively. The correlations between gut microbes and their metabolites were evaluated by Spearman correlation coefficients. The results indicated that phloretin reshaped the disturbed faecal metabolite profile in UC mice and improved the metabolic pathways by balancing the composition of faecal metabolites such as norepinephrine, mesalazine, tyrosine, 5-acetyl-2,4-dimethyloxazole, and 6-acetyl-2,3-dihydro-2-(hydroxymethyl)-4(1H)-pyridinone. Correlation analysis identified the relations between the gut microbes and their metabolites. Proteus was negatively related to many faecal metabolites, such as norepinephrine, L-tyrosine, laccarin, dopamine glucuronide, and 5-acetyl-2,4-dimethyloxazole. The abundance of unidentified Bacteriodales_S24-7_group was positively related to ecgonine, 15-KETE and 6-acetyl-2,3-dihydro-2-(hydroxymethyl)-4(1H)-pyridinone. The abundance of Christensenellaceae_R-7_group was negatively related to the levels of 15-KETE and netilmicin. Stenotrophomonas and 15-KETE were negatively related, while Intestinimonas and alanyl-serine were positively related. In conclusion, phloretin treatment had positive impacts on faecal metabolites in UC mice, and the changes in faecal metabolites were closely related to the gut microbiota.

The protective effect of hypoxic therapy on paraquat-induced toxicity rat model (백서를 이용한 고독성 제초제 파라쿼트 중독 치료를 위한 저농도산소요법의 효과 연구)

  • Kim, Hoon;Min, Jin-Hong;Han, Kyu-Hong;Kang, Joon-Ho
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.15 no.4
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    • pp.2189-2198
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    • 2014
  • Paraquat (PQ) is a very effective and widely used herbicide that was commercially introduced in 1962. In this study, instead of using antioxidants like in the past, to inhibit the formation of PQ-induced ROS, we attempted to reduce the oxygen concentration by using non-lethal hypoxia therapy. Therefore, we studied the toxicity of PQ in vivo, analyzed the major effects of ROS on the targeted lung tissue and compared the results with the gross histological changes after the cell protective effect of non-lethal hypoxia therapy. In vivo studies demonstrated that low-concentration oxygen therapy (i.e., 10-12% oxygen) in rats administered with PQ was associated with a higher survival rate than in rats that received only PQ. In vivo non-lethal hypoxia treatment showed better survival and less lung tissue damage. Using a hypoxic/anaerobic incubator with integrated multifaceted molecular analysis, including MDA assay, glutathione assay, and SOD assay, we established an optimal, significantly reduced in vivo non-lethal hypoxia treatment by exploiting the PQ-induced cytotoxicity responses.

35-Year Research History of Cytotoxicity and Cancer: a Quantitative and Qualitative Analysis

  • Farghadani, Reyhaneh;Haerian, Batoul Sadat;Ebrahim, Nader Ale;Muniandy, Sekaran
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3139-3145
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    • 2016
  • Cancer is the leading cause of morbidity and mortality worldwide, characterized by irregular cell growth. Cytotoxicity or killing tumor cells that divide rapidly is the basic function of chemotherapeutic drugs. However, these agents can damage normal dividing cells, leading to adverse effects in the body. In view of great advances in cancer therapy, which are increasingly reported each year, we quantitatively and qualitatively evaluated the papers published between 1981 and December 2015, with a closer look at the highly cited papers (HCPs), for a better understanding of literature related to cytotoxicity in cancer therapy. Online documents in the Web of Science (WOS) database were analyzed based on the publication year, the number of times they were cited, research area, source, language, document type, countries, organization-enhanced and funding agencies. A total of 3,473 publications relevant to the target key words were found in the WOS database over 35 years and 86% of them (n=2,993) were published between 2000-2015. These papers had been cited 54,330 times without self-citation from 1981 to 2015. Of the 3,473 publications, 17 (3,557citations) were the most frequently cited ones between 2005 and 2015. The topmost HCP was about generating a comprehensive preclinical database (CCLE) with 825 (23.2%) citations. One third of the remaining HCPs had focused on drug discovery through improving conventional therapeutic agents such as metformin and ginseng. Another 33% of the HCPs concerned engineered nanoparticles (NPs) such as polyamidoamine (PAMAM) dendritic polymers, PTX/SPIO-loaded PLGAs and cell-derived NPs to increase drug effectiveness and decrease drug toxicity in cancer therapy. The remaining HCPs reported novel factors such as miR-205, Nrf2 and p27 suggesting their interference with development of cancer in targeted cancer therapy. In conclusion, analysis of 35-year publications and HCPs on cytotoxicity in cancer in the present report provides opportunities for a better understanding the extent of topics published and may help future research in this area.

The Preference Analysis of Forest Therapy Program with regard to MBTI Personality Types (MBTI 성격유형에 따른 산림치유 프로그램 선호도에 관한 연구)

  • Kim, Youn-Hee;Kim, Dong-Jun;Kim, Eun-Jin;Yeoun, Pyung-Sik;Choi, Byung-Jin;Kim, Jea-Kean;Kim, Youn-Soo
    • Korean Journal of Environment and Ecology
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    • v.29 no.3
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    • pp.485-498
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    • 2015
  • The need for forest therapy programs has been increasing. For more effective forest healing, it is necessary to identify the characteristics of participants and develop and operate more targeted and differentiated forest therapy programs accordingly. In this study, the relationships between MBTI (Myers-Briggs Type Indicator) personality types and the relationship between the temperaments of MBTI and the preference for the forest therapy programs were analyzed respectively in pursuit of the basic data required for the effective development and operation of forest healing on the basis of individual characteristics. The survey on the forest therapy program and MBTI personality tests were conducted for 245 normal adults. Using the SPSS 21.0 program analysis, data were analyzed by Analysis of variance (ANOVA) to obtain the difference of preference on the forest therapy program according to the personality type. The Extraversion(E)-Introversion(I) types showed differences in technique-based breathing exercises, walking in the forest(wearing shoes), laughter therapy in the forest, viewing the forest, forest bathing, wind bathing and sun bathing. And the Sensing(S)-iNtuition (N) types had marked differences in listening to the sound of water flowing, drinking herbal tea and sleeping in the forest. The Thinking (T) -Feeling (F) types marked differences in soaking hands and feet in water and sleeping in the forest. The Judging (J)-Perceiving (P) types had differences in vision quest and viewing the forest, respectively, in statistics. Depending on the temperament of the character, there were statistically significant differences in preferences such as drinking herbal tea, eating natural food, sleeping in the forest, viewing the forest and listening to the forest commentary. The results of this study are expected to be used as a basis for forest healing program development and operation.

Assessment of Appropriateness of Standard for Insurance Coverage on Chemotherapy used in Non-small Cell Lung Cancer (NSCLC) (비소세포폐암에 사용되는 항암화학요법의 요양급여기준 적절성 평가)

  • Kim, Jeong-Yeon;Park, Eun-Ji;Bae, Min-Kyung;Yoon, Jeong-Hyun
    • Korean Journal of Clinical Pharmacy
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    • v.21 no.3
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    • pp.193-207
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    • 2011
  • Purpose: The purpose of this study is to assess appropriateness of current standard for insurance coverage by Health Insurance Review & Assessment Service (HIRA) on chemotherapy used in the treatment of advanced non-small cell lung cancer (NSCLC), by reviewing a variety of clinical evidences, and thereby, if needed, to propose an updated evidence-based recommendations. Methods: We collected data from HIRA regarding on the insurance standard which includes the scope and conditions for coverage on systemic chemotherapy of NSCLC. We performed a search for clinical databases and examined the most current clinical evidence from clinical literature including various clinical practice guidelines. Based on the collected data the appropriateness of HIRA standard for insurance coverage of chemotherapy of NSCLC was assessed. Results: Collected data demonstrated that HIRA standard did not reflect the most current clinical practice and evidence. Some were inappropriately listed in HIRA formulary and accepted as a chemotherapy being covered by insurance, despite the lack of evidences of clinical efficacy or superiority over other chemotherapeutic agents or regimens. In addition, there seems to be a need for a modification on the standard for insurance coverage of certain newer chemotherapeutic agents based on the current accumulated data showing their clinical efficacy and benefits in the selected group of NSCLC patients. Therefore, we concluded that current HIRA standard for insurance coverage on chemotherapy of NSCLC needs to be revised and we proposed an updated recommendation based on these latest clinical evidences. Conclusion: The standard for insurance coverage of chemotherapy should be continually examined its appropriateness based on the most recent clinical evidences in a timely manner so as to provide the most effective and safe therapy to cancer patients.

Recovery of Genes Epigenetically Altered by the Histone Deacetylase Inhibitor Scriptaid and Demethylating Agent 5-Azacytidine in Human Leukemia Cells

  • Park, Eun-Kyung;Jeon, Eun-Hyung;Kim, In-Ho;Park, Seon-Yang
    • Genomics & Informatics
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    • v.8 no.4
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    • pp.185-193
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    • 2010
  • Histone deacetylation and demethylation are epigenetic mechanisms implicated in cancer. Studies regarding the role of modulation of gene expression utilizing the histone deacetylase inhibitor scriptaid and the demethylating agent 5-azacytidine in HL-60 leukemia cells have been limited. We studied the possibility of recovering epigenetically silenced genes by scriptaid and 5-azacytidine in human leukemia cells by DNA microarray analysis. The first group was leukemia cells that were cultured with 5-azacytidine. The second group was cultured with scriptaid. The other group was cultured with both agents. Two hundred seventy newly developed genes were expressed after the combination of 5-azacytidine and scriptaid. Twenty-nine genes were unchanged after the combination treatment of 5-azacytidine and scriptaid. Among the 270 genes, 13 genes were differed significantly from the control. HPGD, CPA3, CEACAM6, LOC653907, ETS1, RAB37, PMP22, FST, FOXC1, and CCL2 were up-regulated, and IGLL3, IGLL1, and ASS1 were down-regulated. Eleven genes associated with oncogenesis were found among the differentially expressed genes: ETS1, ASCL2, BTG2, BTG1, SLAMF6, CDKN2D, RRAS, RET, GIPC1, MAGEB, and RGL4. We report the results of our leukemia cell microarray profiles after epigenetic combination therapy with the hope that they are the starting point of selectively targeted epigenetic therapy.

Needs Assessment of Nutrition Programs in Public Health Center by General Characteristics and Body Mass Index of Community Residents (지역사회 주민의 일반적 특성 및 체질량 지수에 따른 보건소 영양사업 요구도 평가)

  • Joung Hyojee;Ahn Byung Chul
    • Korean Journal of Community Nutrition
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    • v.10 no.1
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    • pp.122-131
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    • 2005
  • The purpose of this study was to assess the needs for nutrition programs in the public health centers by general characteristics and body mass index (BMI) of community residents. Information of general characteristics of study participants including age, education, income, marital status, residence, and job, and resident's interest in nutrition programs, the preferred educational methods and the willingness to participate in nutrition programs were collected by an interview. Weight and height were measured and were used to calculate the BMI. The program that resident's were most interested in was 'diet therapy for chronic disease and counseling' ($28.5\%$), followed by 'nutritional management for the elderly' ($21.1\%$), and 'obesity and weight control' ($17.1\%$). 'Education and counseling by nutrition professionals' was the most preferred educational method. Among the programs that the subjects would participate in, if they were offered in public health centers, $65.8\%$ subjects would participate in 'diet therapy for chronic disease and counseling' programs, $64.9\%$ would participate in 'nutritional management for the elderly' programs and $52.2\%$ would participate in 'obesity and weight control' programs. The contents of programs that the subjects were interested in, the preferred methods and their willingness to participate nutrition programs differed significantly by age, income, education, marital status, and body mass index. The results imply that the planning of nutrition interventions in the public health centers must be tailored and targeted group specific by taking the participants general characteristics and body mass index into consideration. This would surely increase the nutrition program's effectiveness

Evaluation of Quantitative Effectiveness of MR-DTI Analysis with and without Functional MRI (기능적 자기공명영상 사용유무에 따른 확산텐서영상 분석의 유효성 평가)

  • Lee, Dong-Hoon;Park, Ji-Won;Hong, Cheol-Pyo
    • The Journal of Korean Physical Therapy
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    • v.25 no.5
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    • pp.260-265
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    • 2013
  • Purpose: This study was conducted in order to evaluate the quantitative effectiveness of region of interest (ROI) setting in MR-DTI analysis with and without fMRI activation results. Methods: Ten right-handed normal volunteers participated in this study. DTI and fMRI datasets for each subject were obtained using a 1.5T MRI system. For neural fiber tracking, ROIs were drawn using two methods: The drawing points were located in the fMRI activation areas or areas randomly selected by users. In this study, the neural fiber tract targeted the corticospinal tract (CST) Quantitative analyses were performed and compared. The pixel numbers passing through the fiber tract in the individual brain volume were counted. The ratios between the ROI pixel numbers and the extracted fiber pixel numbers, and the ratios between the fiber pixel numbers and the whole-brain pixel numbers were also calculated. Results: According to our results, extracted CST fiber tract in which the ROI was drawn with fMRI activation areas showed higher distribution than drawing the ROI by users' hands. In addition, the quantitatively measured values represented higher pixel distribution: The counted average pixel numbers were 4553.8 and 1943.3. The average ratios of the ROI areas were 33.87 and 22.52. The average percentages of the individual whole-brain volume numbers were 2.06 and 0.87. Conclusion: Results of this study appear to indicate that use of this method can allow for more objectives and significant for study of the recovery of neural fiber mechanisms and brain rehabilitation.