• Title/Summary/Keyword: antineoplastic drug

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Ganodermanontriol Suppresses the Progression of Lung Adenocarcinoma by Activating CES2 to Enhance the Metabolism of Mycophenolate Mofetil

  • Qingfeng Xie;Zhuo Cao;Weiling You;Xiaoping Cai;Mei Shen;Zhangyong Yin;Yiwei Jiang;Xin Wang;Siyu Ye
    • Journal of Microbiology and Biotechnology
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    • v.34 no.2
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    • pp.249-261
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    • 2024
  • New anti-lung cancer therapies are urgently required to improve clinical outcomes. Since ganodermanontriol (GDNT) has been identified as a potential antineoplastic agent, its role in lung adenocarcinoma (LUAD) is investigated in this study. Concretely, lung cancer cells were treated with GDNT and/or mycophenolate mofetil (MMF), after which MTT assay, flow cytometry and Western blot were conducted. Following bioinformatics analysis, carboxylesterase 2 (CES2) was knocked down and rescue assays were carried out in vitro. Xenograft experiment was performed on mice, followed by drug administration, measurement of tumor growth and determination of CES2, IMPDH1 and IMPDH2 expressions. As a result, the viability of lung cancer cells was reduced by GDNT or MMF. GDNT enhanced the effects of MMF on suppressing viability, promoting apoptosis and inducing cell cycle arrest in lung cancer cells. GDNT up-regulated CES2 level, and strengthened the effects of MMF on down-regulating IMPDH1 and IMPDH2 levels in the cells. IMPDH1 and IMPDH2 were highly expressed in LUAD samples. CES2 was a potential target for GDNT. CES2 knockdown reversed the synergistic effect of GDNT and MMF against lung cancer in vitro. GDNT potentiated the role of MMF in inhibiting tumor growth and expressions of CES2 and IMPDH1/2 in lung cancer in vivo. Collectively, GDNT suppresses the progression of LUAD by activating CES2 to enhance the metabolism of MMF.

Anti-Cancer Effect of the Combination of Thiacremonone and Docetaxel by Inactivation of NF-κB in Human Cancer Cells

  • Ban, Jung-Ok;Cho, Jin-Suk;Hwang, In-Guk;Noh, Jin-Woo;Kim, Wun-Jae;Lee, Ung-Soo;Moon, Dong-Cheul;Jeong, Heon-Sang;Lee, Hee-Soon;Hwang, Bang-Yeon;Jung, Jae-Kyung;Han, Sang-Bae;Hong, Jin-Tae
    • Biomolecules & Therapeutics
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    • v.17 no.4
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    • pp.403-411
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    • 2009
  • Thiacremonone, the main component isolated from heated garlic (Allium sativum L.), is interested for using as a cancer preventive or therapeutic agent since garlic has been known to be useful plant in the treatment of cancers. Nuclear factor kappaB (NF-${\kappa}B$) is constitutively activated in the prostate cancer and activation of NF-${\kappa}B$ is implicated in drug resistance in cancer cells. Docetaxel, a semisynthetic analog of paclitaxel, is an antineoplastic drug widely used for advanced various cancer. In previous studies, we found that thiacremonone inhibited activation of NF-${\kappa}B$ in cancer cells and marcrophages. In the present study, we investigated whether thiacremonone could increase susceptibility of prostate cancer cells (PC-3 and DU145) to docetaxel via inactivation of NF-${\kappa}B$. We found that the combination treatment of thiacremonone (50 ${\mu}g$/ml) with docetaxel (5 nM) was more effective in the inhibition of prostate cancer cell growth and induction of apoptosis accompanied with the significant inhibition of NF-${\kappa}B$ activity than those by the treatment of thiacremonone or docetaxel alone. It was also found that NF-${\kappa}B$ target gene expression of Bax, caspase-3 and caspase-9 was much more significantly enhanced, but the expression of Bcl-2 was also much more significantly inhibited by the combination treatment. These results indicate that thiacremonone inhibits NF-${\kappa}B$, and enhances the susceptibility of prostate cancer cells to docetaxel. Thus, thiacremonone could be useful as an adjuvant anti-cancer agent.

Apoptotic Response of Human Oral Squamous Carcinoma Cells to Etoposide (Etoposide에 대한 사람구강편평상피암종세포의 세포자멸사 반응)

  • Kim, Gyoo-Cheon;Lee, Kyoung-Duk;Park, Jae-Hyun;Kim, Duk-Han;Park, Jeong-Kil;Park, June-Sang;Park, Bong-Soo
    • Journal of Oral Medicine and Pain
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    • v.30 no.2
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    • pp.231-238
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    • 2005
  • Anti-cancer drugs have been shown to target diverse cellular functions in mediation cell death in chemosensitive tumors. Most antineoplastic drugs used in chemotherapy of leukemias and solid tumors induce apoptosis in drug-sensitive target cells. However, the precise molecular requirements that are central for drug-induced cell death are largely unknown. Etoposide is used for the treatment of lung and testicular cancer. This study was performed to examine whether etoposide promote apoptosis in human oral squamous carcinoma cells (OSC9) as well as in lung and testicular cancer. Etoposide had a significant dose- and time-dependent inhibitory effect on the viability of OSC9 cells. TUNEL assay showed the positive reaction on condensed nuclei. Hoechst stain demonstrated that etoposide induced a change in nuclear morphology. The expression of p53 was increased at 48 hour, suggesting that the nuclear of OSC9 cell was damaged, thereby inducing apoptosis. Etoposide treatment induced caspase-3 cleavage and activation. Intact PARP protein 116-kDa and 85-kDa cleaved product were observed. The activated caspase-3 led cleavage of the PARP. These results demonstrate that etoposide-induced apoptosis in OSC9 cells is associated with caspase-3 activation.

Usefulness of cyclic thermal therapy and red blood cell scintigraphy in patients with chemotherapy-induced peripheral neuropathy

  • Kim, Minjoo;Kim, Eun-Mi;Oh, Phil-Sun;Lim, Seok Tae;Sohn, Myung-Hee;Song, Eun-Kee;Park, Keon Uk;Kim, Jin Young;Won, Kyoung Sook;Jeong, Hwan-Jeong
    • The Korean Journal of Pain
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    • v.34 no.4
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    • pp.427-436
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    • 2021
  • Background: Pharmacological and non-pharmacological therapies have been used to treat patients with chemotherapy-induced peripheral neuropathy (CIPN). However, the effect of therapies in cancer patients has yet to be investigated comprehensively. We hypothesized that cyclic thermal therapy would improve blood flow and microcirculation and improve the symptoms driven by CIPN. Methods: The criteria of assessment were blood volume in region of interest (ROI) in the images, and European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 questionnaire scores. The blood volume was quantified by using red blood cell (RBC) scintigraphy. All patients were treated 10 times during 10 days. The thermal stimulations, between 15° and 41°, were repeatedly delivered to the patient's hands. Results: The total score of the questionnaires, the score of questions related to the upper limbs, the score of questions closely related to the upper limbs, and the score excluding the upper limbs questions was decreased. The blood volume was decreased, and the variance of blood volume was decreased. During cooling stimulation, the blood volume was decreased, and its variance was decreased. During warming stimulation, the blood volume was decreased, and its variance was decreased. Conclusions: We suggest that cyclic thermal therapy is useful to alleviate CIPN symptoms by blood circulation improvement. RBC scintigraphy can provide the quantitative information on blood volume under certain conditions such as stress, as well as rest, in peripheral tissue.

Guideline of Improvement and Evaluation of Prescribing Errors in Colorectal Chemotherapy (대장암 항암 화학요법의 처방 오류 평가 및 개선안 제시)

  • Lim, Hyun-Soo;Lim, Sung Cil
    • Korean Journal of Clinical Pharmacy
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    • v.23 no.2
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    • pp.158-166
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    • 2013
  • Background: Colorectal cancer shows a significant increase in South Korea due to westernization of diet, lack of dietary fiber, drinking and smoking, irregular defecation. There are surgery, chemotherapy, radiation therapy in treatment of colorectal cancer. There may be a medication errors in the process of chemotherapy because of its high toxicity, narrow therapeutic index and the health status of cancer patients. Consequently medication errors can cause increasing the risk of death, prolonging hospital stay and increasing the cost. Among medication errors on medication use process, prescribing errors are of particular concern due to higher risk of serious consequences. It is important for pharmacist to prevent the prescribing errors before reaching patient. Therefore we analyzed the prescriptions of colorectal cancer, classified prescribing errors, suggested guideline to reduce prescribing errors and verified the importance of pharmacist's role in prevention of medication errors activity. Methods: We collected the numbers of prescriptions of colorectal cancer(n=2,373) through anti cancer management program and EMR and analyzed the errors of prescriptions by categories from Oct 1st 2011 to Sep 30th 2012 at Chungbuk National University Hospital. We reviewed the prescriptions as follows - patients' characteristics, the result of test, previous prescriptions, characteristics of antineoplastic agents and patients' allergy, drug sensitivity, adverse events. Prescriptions are classified into inpatient and outpatient and analyzed the errors of prescriptions by categories (dosage form, dose, input, diluents, regimen, product). Results: Total prescription number of inpatient and outpatient of colorectal cancer was 1,193 and 1,180 and that of errors was 107(9%) and 22(1.9%), respectively. In case of errors of categories, the number of errors of dosage form is 69 and 8, errors of dose is 15 and 5, errors of input is 9 and 9 in inpatient and outpatient prescriptions, respectively. Errors of diluents is 8, errors of regimen is 3, errors of product is 3 in only inpatient prescriptions. In case of errors of categories by inpatient department, the number of errors of dosage form is 34 and 35, errors of dose is 7 and 8, errors of input is 6 and 3, errors of diluents is 4 and 4, errors of regimen is 2 and 1, errors of product is 2 and 1 in SG and HO, respectively. In case of outpatient department, the number of errors of dosage form is 8 in HO, errors of dose is 5 in HO, errors of input is 5 and 4 in SG and HO, respectively. Conclusions: The rate of errors of inpatient is higher than that of outpatient. Junior doctors are engaged in prescriptions of inpatient and pharmacist need to pay attention to review all prescriptions. If prescribing errors are discovered, pharmacist should contact the prescriber and correct the errors without delay. The guideline to reduce prescribing errors might be upgrading software of anti cancer management program, education for physicians as well as pharmacists and calling prescriber's attention to preventing recurrence of errors.

Anti-Angiogenic Activity of Gecko Aqueous Extracts and its Macromolecular Components in CAM and HUVE-12 Cells

  • Tang, Zhen;Huang, Shu-Qiong;Liu, Jian-Ting;Jiang, Gui-Xiang;Wang, Chun-Mei
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.2081-2086
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    • 2015
  • Gecko is a kind of traditional Chinese medicine with remarkable antineoplastic activity. However, undefined mechanisms and ambiguity regarding active ingredients limit new drug development from gecko. This study was conducted to assess anti-angiogenic properties of the aqueous extracts of fresh gecko (AG) or macromolecular components separated from AG (M-AG). An enzyme-linked immunosorbent assay (ELISA) approach was applied to detect the vascular endothelial growth factor (VEGF) secretion of the tumor cells treated with AG or M-AG. The effect of AG or M-AG on vascular endothelial cell proliferation and migratory ability was analyzed by tetrazolium dye colorimetric method, transwell and wound-healing assays. Chick embryo chorioallantoic membrane (CAM) assays were used to ensure the anti-angiogenic activity of M-AG in vivo. The results showed that AG or M-AG inhibited the VEGF secretion of tumor cells, the relative inhibition rates of AG and M-AG being 27.2% and 53.2% respectively at a concentration of $20{\mu}L/mL$. AG and M-AG inhibited the vascular endothelial (VE) cell proliferation with IC50 values of $11.5{\pm}0.5{\mu}L/mL$ and $12.9{\pm}0.4{\mu}L/mL$ respectively. The VE cell migration potential was inhibited significantly (p<0.01) by the AG (${\geq}24{\mu}L/mL$) or M-AG (${\geq}12\mu}L/mL$) treatment. In vivo, neovascularization of CAM treated with M-AG was inhibited significantly (p<0.05) at a concentration of ${\geq}0.4{\mu}L/mL$. This study provided evidence that anti-angiogenesis is one of the anti-tumor mechanisms of AG and M-AG, with the latter as a promising active component.

A Case of Recurrent Pneumonitis Caused by Bojungikgitang (Bu-Zhong-Yi-Qi-Tang) (보중익기탕(補中益氣湯) 복용 후 재발생한 미만성 간질성 폐렴 1예)

  • Kim, Seung Gu;Kang, Gun Hi;Kim, Jun Jae;Park, Hyun;Baek, Na Na;Choi, Sang Bong;Shin, Eun Ah;Kim, Joung Sook;Park, I Nae;Jeung, Hoon;Hur, Jin Won;Lee, Sung Soon;Lee, Hyun Kyung;Kim, Joo In;Lee, Young Min;Lee, Hyuk Pyo;Yum, Ho Kee;Choi, Soo Jeon
    • Tuberculosis and Respiratory Diseases
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    • v.65 no.5
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    • pp.416-420
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    • 2008
  • Many classes of drug, such as antineoplastic drugs and antiarrhythmic drugs, have potential to induce interstitial lung disease. Herbal medicines are also believed to have the potential to induce pneumonitis. However, to our knowledge, there are no reports of pneumonitis caused by herbal medications in the Korean medical database. We report a case of recurrent pneumonitis caused by a self rechallenge of the Herbal medicine Bojungikgitang (Bu-Zhong-Yi-Qi-Tang : Hochu-ekki-to).

Preventive effect of fermented red ginseng on cisplatin-induced nephrotoxicity mouse (Cisplatin으로 유도된 신손상 마우스 모델에 대한 발효홍삼의 예방효능)

  • Hyun, Ja-Kyoung;Kwon, O Jun;Lee, Joo Young;Roh, Seong-Soo;Seo, Young-Bae
    • Journal of Applied Biological Chemistry
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    • v.59 no.2
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    • pp.113-124
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    • 2016
  • Red ginseng is known to have many beneficial effects. Cisplatin, an effective antineoplastic drug, can cause many side effects like irreversible sensorineural hearing loss and serious tinnitus in humans. This study is aimed to reduce a cisplatin's side effect, nephrotoxicity by fermentated korean red ginseng. Korea ginseng was produced by steaming and dring and fermentation. And mice were divided into 4 groups- (A) normal mice, (B) Vehicle treated cisplatin mice, (C) RG0F0-treated cisplatin mice, (D) RG8F3-treated cisplatin mice. C and D groups were feed each material 200 mg/kg/day during 4 days. And cisplatin 20 mg/kg injected to B, C, and D groups as abdominal injection. After 24 h, blood sample was collected. The kidneys were harvested for histological, immuno histochemical and western blot analysis. 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity was depended on steaming hours. RG0F0 and RG8F3 (ginseng-8 h steamed and fermented by Saccharomyces cerevisiae) were showed antioxidants effect in DPPH and ABTS radical scavenging activity. Component amounts according to steaming hours. 8 h steamed red ginseng had the most ingredients of ginsenoside. Treatments with RG8F3 reduced cisplatin-induced nephrotoxicity in the mice resulting in increase of GSH and decrease of ROS, BUN, creatinine, and inflammatory mediators. This result seems to be involved with the restriction of the inflammation in the kidney. Therefore, fermented red ginseng might have therapeutic efficacy in reduce kidney injury induced by cisplatin treatment.

1-β-D-Arabinofuranosyl-cytosine Induces Chromosomal Breaks in vitro (In vitro에서 1-β-D-arabinofuranosyl-cytosine의 염색체 파열 유도)

  • Jeon, In-sang
    • Clinical and Experimental Pediatrics
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    • v.46 no.12
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    • pp.1186-1193
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    • 2003
  • Purpose : Fragile sites are points on chromosomes which tend to break non-randomly when exposed to specific chemical agents or conditions of tissue culture. The chromosomal break induced by the antineoplastic drug, 1-${\beta}$-D-arabinofuranosyl-cytosine(Ara-c), was investigated to study the laboratory conditions in which the incidence of chromosomal break could be enhanced. Besides, the fragile sites induced by Ara-C were investigated and compared to the already known locations of the specific chromosomal alterations observed in specific neoplasms. Methods : T-lymphocytes from theree normal males and three females were cultured for 48 hours. Cells from each individual were exposed to the Ara-C for an additional 24 hours. After the caffeine was added during the last six hours culture, the metaphase chromosomes were prepared following the conventional method. A site was considered fragile if it was found to break two or more per 100 chromosomal breaks in more than four of six individuals tested. Results : Ara-C induced 252.1 chromosomal breaks per 100 mitotic cells and this result was significantly higher than that of the control, which induced 25.2 breaks(P<0.05). The incidence of the chromosomal break by Ara-C was higher, if cultured in the MEM-FA, which has no folic acid, than in the RPMI 1640 which contains enough folic acid(P<0.05). The most common break site by Ara-C was 3p14.2(FRA3B). There were 20 fragile sites induced by Ara-C. Among these 20 fragile sites, seven coincided with the locations of the mapped oncogenes, JUN, SKI, REL, N-MYC, FHIT, MET, ETS-1, and FOS. Conclusion : S phase specific chemotherapeutic agent, Ara-C, induced the expression of the chromosomal fragile sites effectively using the T-lymphocyte in vitro. Some of the fragile sites by Ara-C highly coincided with the oncogenes and neoplasm specific chromosome breakpoints. In this regard, the fragile sites reported here could provide the unknown neoplasm related chromosomal alternation points.