• 제목/요약/키워드: Primary drug resistance

검색결과 63건 처리시간 0.031초

MiR-130a Overcomes Gefitinib Resistance by Targeting Met in Non-Small Cell Lung Cancer Cell Lines

  • Zhou, Yong-Ming;Liu, Juan;Sun, Wei
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권3호
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    • pp.1391-1396
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    • 2014
  • Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the most common cause of lung cancer death. Currently, the epidermal growth factor receptor inhibitor gefitinib is used for its treatment; however, drug resistance is a major obstacle. Expression of Met has been associated with both primary and acquired resistance to gefitinib, but the mechanisms regulating its expression are not fully understood. Recently, miRNAs such as miR-130a have been shown to play a role in gefitinib resistance, but importance in NSCLC and relationships with Met have not been fully explored. Here we show that miR-130a is over-expressed in gefitinibsensitive NSCLC cell lines, but is low in gefitinib-resistant NSCLC cell lines. Moreover, miR-130a expression was negatively correlated with that of Met. Further analysis revealed that over-expression of miR-130a increased cell apoptosis and inhibited proliferation of NSCLC cells treated with gefitinib, whereas lowering the expression of miR-130a decreased cell apoptosis and promoted cell proliferation after treatment with gefitinib in both gefitinib-sensitive and -resistant NSCLC cell lines, suggesting that miR-130a overcomes gefitinib resistance. We also demonstrated that miR-130a binds to the 3'-UTR of Met and significantly suppresses its expression. Finally, our results showed that over-expressing Met could "rescue" the functions of miR-130a regarding cell apoptosis and proliferation after cells are treated with gefitinib. These findings indicate that the miR-130a/Met axis plays an important role in gefitinib resistance in NSCLC. Thus, the miR-130a/Met axis may be an effective therapeutic target in gefitinib-resistant lung cancer patients.

재치료 폐결핵환자의 임상적 세균학적 특성 (Clinical and Bacteriologic Characteristics of Retreated Tuberculosis Patients)

  • 오승준;윤기헌;유지홍;강홍모
    • Tuberculosis and Respiratory Diseases
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    • 제42권1호
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    • pp.19-24
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    • 1995
  • 연구배경: 폐결핵은 처음 발병하였을 때 표준처방에 의하여 적절히 치료하면 대부분 완치할 수 있는 질환이나 실제로 상당수의 환자들이 부적절한 치료를 함으로써 악화되고 장기적인 치료를 받는 경우가 있다. 또한 약제 내성이 발생할 경우 초치료 약제보다 항균력이 약한 약제들로 치료하게 됨으로써 치료기간이 길어짐은 물론 정상적인 생활을 하지 못할 정도로 심한 장애를 초래하거나 사망하는 경우까지도 있다. 방법: 저자등은 초치료에 실패하거나 재발한 폐결핵 환자들의 특성과 문제점을 알아보고자 1986년 3월부터 90년 2월까지 입원하여 치료한 폐결핵환자 484명 가운데 94명의 재치료 환자들의 기록을 조사하여 다음과 같은 결과를 얻었다. 결과: 1) 총 재치료환자 94명중 남자 62명, 여자 32명이며 평균연령은 남자 $51.43{\pm}15.56$, 여자 $45.00{\pm}18.40$세 이었다. 2) 흉부엑스선상 경증이 10명(11.1%), 중등도가 31명(33.3%), 중증이 52명(55.6%)이었다. 3) 객담내 균양성환자가 73명 이었다. 4) 약제감수성검사를 시행한 42명중 1제 내성자가 9명(20.5%), 2제 내성자가 18명(40.8%), 3제이상 내성자가 14명(31.8%)이었다. 5) 표준처방에 의한 초치료를 완료하지 못하였던 경우가 41명(43.6%)이었으며 재치료시 완치한 환자는 24명(25.5%)에 불과한 반면 도중에 환자가 치료를 포기한 경우가 39명(41.6%)나 되었다. 결론: 재치료시 중요한 치료실패 원인은 환자의 중도탈락 이었으며, 따라서 초치료 및 재치료시 철저한 환자관리가 이루어져야 할것으로 생각된다.

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AP-PCR을 이용한 다제내성 Staphylococcus aureus의 유전형 분석 (Genotypic Analysis of Multi-drug Resistant Staphylococcus aureus by Arbitrarily Primed Polymerase Chain Reaction)

  • 신경현;홍승복;손승렬
    • 대한임상검사과학회지
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    • 제36권2호
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    • pp.89-97
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    • 2004
  • Many strains of Staphylococcus aureus were isolated from pus samples from primary, secondary, and tertiary medical institutions and were subjected to an antibiotic sensitivity test. Ciprofloxacin, clindamycin, erythromycin, gentamicin, oxacillin penicillin, tetracycline, trimethoprim/sulfamethoxazole, vancomycin and teicoplanin were used for the antibiotic sensitivity test. The strains showed hightest resistance to penicillin(91%), but all of strains tested were susceptible to vancomycin and teicoplanin. The isolated multi-drug(penicillin-tetracycline-ciprofloxacin-clindamycin-erythromycin- oxacillin-gentamicin) resistant S. aureus were analyzed genotypically using an AP-PCR(Arbitrarily Primed polymerase chain reaction) with an arbitrary 3 primers. Based on the result for genotype analysis, the genotypes identified by S1 primer did not coincide with those of S2 or E2 primers. Genotypes identified by S2 primer did not coincide with those of S1 or E2 primers. Also genotypes identified by the E2 primer did not coincide with those of S1 or S2 primers. Therefore, an analysis of AP-PCR test with multiple primers will provide more sensitive identification. A strain from a secondary medical institution and a strain from a tertiary medical institution which showed the same genotype for S1, S2, and E2 primers are required for further epidemiological study.

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Galectin-1 Promotes Gastric Carcinoma Progression and Cisplatin Resistance Through the NRP-1/c-JUN/Wee1 Pathway

  • Zhengyang Pan;Guoxi Xu;Yan Zhang;Meiling Wu;Jiahui Yu;Xujun He;Wei Zhang;Junfeng Hu
    • Journal of Gastric Cancer
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    • 제24권3호
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    • pp.300-315
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    • 2024
  • Purpose: Gastric cancer (GC) is among the deadliest malignancies and the third leading cause of cancer-related deaths worldwide. Galectin-1 (Gal-1) is a primary protein secreted by cancer-associated fibroblasts (CAFs); however, its role and mechanisms of action of Gal-1 in GC remain unclear. In this study, we stimulated GC cells with exogenous human recombinant galectin-1 protein (rhGal-1) to investigate its effects on the proliferation, migration, and resistance to cisplatin. Materials and Methods: We used simulated rhGal-1 protein as a paracrine factor produced by CAFs to induce GC cells and investigated its promotional effects and mechanisms in GC progression and cisplatin resistance. Immunohistochemical (IHC) assay confirmed that Gal-1 expression was associated with clinicopathological parameters and correlated with the expression of neuropilin-1 (NRP-1), c-JUN, and Wee1. Results: Our study reveals Gal-1 expression was significantly associated with poor outcomes. Gal-1 boosts the proliferation and metastasis of GC cells by activating the NRP-1/C-JUN/Wee1 pathway. Gal-1 notably increases GC cell resistance to cisplatin The NRP-1 inhibitor, EG00229, effectively counteracts these effects. Conclusions: These findings revealed a potential mechanism by which Gal-1 promotes GC growth and contributes to chemoresistance, offering new therapeutic targets for the treatment of GC.

Isolation and Identification of Bacillus cereus from Fermented Red Pepper-Soybean Paste (Kochujang), and Its Heat Resistance Characteristics

  • Kim, Yong-Suk;Ahn, Yong-Sun;Jeon, Do-Youn;Shin, Dong-Hwa
    • Food Science and Biotechnology
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    • 제17권1호
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    • pp.123-129
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    • 2008
  • To isolate Bacillus cereus presenting at a level of 5 log CFU/g in kochujang, a primary dilution ($10^{-1}$) of kochujang was heated at $85^{\circ}C$ for 5 min. Two isolated strains Voges-Proskauer positive colony (KBC) and a negative colony (KBM) were identified as B. cereus and Bacillus mycoides, respectively, by biochemical test and 16S rDNA sequencing. $D_{100^{\circ}C}$-Values of KBC and KBM strains was 8.37 and 7.08 min, respectively. When spores of KBC strain were inoculated to kochujang at the level of 4-5 log spores/g, the number of spores was no significant difference (p<0.05) for each sample from 1 up to 60 day of aging. When kochujang was inoculated with 4 log spores/g and heated at $85^{\circ}C$ for 15 min, the number of spores was similar to that of unheated kochujang. Therefore, we estimated that B. cereus isolated from kochujang resistant on the heat treatment ($85^{\circ}C$, 15 min) and its heat resistance characteristics could be used to count the number in kochtjang.

Resistance against white spot syndrome virus (WSSV) infection in wild marine crab Gaetice depressus by injection of recombinant VP28 protein

  • Kim, Chun Soo;Choi, Seung Hyuk;Kim, Min Sun;Kim, Ki Hong
    • 한국어병학회지
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    • 제27권1호
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    • pp.11-16
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    • 2014
  • The resistance against white spot syndrome virus (WSSV) infection in wild marine crab Gaetice depressus by the immunization of a recombinant glutathione-S-transferase (GST) fused VP28 protein (GST-VP28) was evaluated. The cumulative mortalities of GST-VP28 injected groups were lower than those of the control groups at 10 days of post-challenge, and the time to death of 50% crab ($TD_{50}$) was delayed by the immunization using GST-VP28. The group boosted with GST-VP28 after 2 weeks of primary immunization clearly showed longer $TD_{50}$ than non-boosted group against challenge with WSSV. This result suggests that boosting with the antigen protein elicit stronger immune responses similar to adaptive immune responses of vertebrates. However, the short $TD_{50}$ was observed in the group challenged at 3 weeks post boosting comparing to the group challenged at 1 week post boosting. This suggests that the protective strength of immunization decreased by the time.

Staphylococcus Species in the Dental and Medical Environment

  • Han, Seung-Ho;Kim, Shin-Moo;Jeong, Seung-Il;Kim, Kang-Ju
    • International Journal of Oral Biology
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    • 제38권1호
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    • pp.1-4
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    • 2013
  • Staphylococcus species are one of prevalent pathogens found in hospitals. Microbes that are a primary cause of nosocomial infection were isolated from a dental and medical environment it may assist the reader to explain what this is and how it differs from the 'dental health care providers and ward health care providers'. To investigate the distribution of staphylococcus species in this environment, we used vitek II to measure drug sensitivity, and further performed biochemical testing. The isolation rate of staphylococcus species from the dental and medical environment was 100% but from dental health care providers and ward health care providers were 44.4% and 33.3%, respectively. In the analyses, staphylococcus species showed resistance to diffusion of cefoxitin and oxacillin discs. These staphylococci may be sufficiently positive for the mecA gene. Our results suggest that staphylococci might be an important cause of nosocomial infection in the dental clinic.

Therapy of Diabetes Mellitus Using Experimental Animal Models

  • Min, T.S.;Park, Soo Hyun
    • Asian-Australasian Journal of Animal Sciences
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    • 제23권5호
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    • pp.672-679
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    • 2010
  • Diabetes mellitus is a worldwide epidemic with high mortality. As concern over this disease rises, the number and value of research grants awarded by the National Research Foundation of Korea (NRF) have increased. Diabetes mellitus is classified into two groups. Type 1 diabetes requires insulin treatment, whereas type 2 diabetes, which is characterized by insulin resistance, can be treated using a variety of therapeutic approaches. Hyperglycemia is thought to be a primary factor in the onset of diabetes, although hyperlipidemia also plays a role. The major organs active in the regulation of blood glucose are the pancreas, liver, skeletal muscle, adipose tissue, intestine, and kidney. Diabetic complications are generally classified as macrovascular (e.g., stroke and heart disease) or microvascular (i.e., diabetic neuropathy, nephropathy, and retinopathy). Several animal models of diabetes have been used to develop oral therapeutic agents, including sulfonylureas, biguanides, thiazolidinediones, acarbose, and miglitol, for both type 1 and type 2 diseases. This review provides an overview of diabetes mellitus, describes oral therapeutic agents for diabetes and their targets, and discusses new developments in diabetic drug research.

신체질환 환자들에서 우울증의 평가 및 치료 (Assessment and Treatment of Depression in the Medically III)

  • 고경봉
    • 정신신체의학
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    • 제9권2호
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    • pp.111-132
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    • 2001
  • 신체질환 환자들에서의 우울증은 일차진료의나 정신과자문의가 흔히 부딪치는 임상적 문제들이다. 본 저자는 이런 환자들을 효과적으로 평가하고 치료하기 위한 방법들을 알아보고자 하였다. 첫째, 환자의 의학적 및 정신과적 상태를 동시에 평가해야 한다. 둘째, 신체질환 환자에서 우울의 평가는 다면적인 접근을 고려하는 것이 바람직하다. 때로는 심리적 도구를 이용하는 것도 좋은 평가 방법이다. 치료는 첫째, 기질적 원인을 찾아서 제거하는 일이 무엇보다 중요하다. 둘째, 정신사회적 치료로는 정신과적 치료에 대한 저항을 다루어야 하고 심한 신체적 질환에 따른 낙담 반응을 처리해 주는 일이다. 셋째, 생물학적인 치료방법으로는 적절한 항우울제를 선택하는 것이 중요하다. 선체질환 환자들에서 항우울제의 선택은 환자의 일차적인 우울증상, 약물역학 및 약물역동, 항우울제의 부작용을 평가한 후 고려한다. 이 외에도 약물-질병 및 약물-약물 상호작용의 가능성에 관해 각별히 주의를 기울일 필요가 있다. SSRI약물, bupropion, venlafaxine과 같은 새로운 항우울제들이 신체질환 환자들의 우울증 치료에 효과적이나 삼환계 항우울제는 통증장애 환자들에서는 아직도 효과적으로 사용될 수 있는 약물이다. 신체질환 환자들에서 항우울제로 우울증이 잘 치료되지 않는 경우에는 전기충격요법의 사용을 고려해 본다.

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Evaluating the Regulation of P-glycoprotein by Phytochemicals Using Caco-2 Cell Permeability Assay System

  • Choi, Ran Joo;Kim, Yeong Shik
    • Natural Product Sciences
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    • 제20권1호
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    • pp.1-6
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    • 2014
  • P-glycoprotein (P-gp) is a permeability glycoprotein also known as multidrug resistance protein 1 (MDR1). P-gp is an ATP-binding cassette (ABC) transporter that pumps various types of drugs out of cells. These transporters reduce the intracellular concentrations of drugs and disturb drug absorption. The Caco-2 cell permeability assay system is an effective in vitro system that predicts the intestinal absorption of drugs and the functions of enzymes and transporters. Rhodamine-123 (R-123) and digoxin are well-known P-gp substrates that have been used to determine the function of P-gp. Efflux of P-gp substrates by P-gp has been routinely evaluated. To date, a number of herbal medicines have been tested with Caco-2 cell permeability assay system to assess bioavailability. There are growing efforts to find phytochemicals that potentially regulate P-gp function. The Caco-2 cell permeability assay system is a primary strategy to search for candidates of P-gp inhibitors. In this mini review, we have summarized the P-gp modulation by herbal extracts, decoctions or single components from natural products using Caco-2 cell permeability assays. Many natural products are known to regulate P-gp and herbal medicines could be used in combination with conventional drugs to enhance bioavailability.