• Title/Summary/Keyword: anti-cancer agents

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Effect of Grape Procyanidins on Tumor Angiogenesis in Liver Cancer Xenograft Models

  • Feng, Li-Li;Liu, Bing-Xia;Zhong, Jin-Yi;Sun, Li-Bin;Yu, Hong-Sheng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.737-741
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    • 2014
  • Background: In recent years a wide variety of flavonoids or polyphenolic substances have been reported to possess substantial anti-carcinogenic and antimutagenic activities. Grape proanthocyanidins (GPC) are considered as good examples for which there is evidence of potential roles as anti-carcinogenic agents. Methods: A xenograft model was established using H22 cells subcutaneously injected into mice and used to assess different concentrations of grape proanthocyanidins (GPC) and Endostar. Treatments were maintained for 10 days, then levels of vascular endothelial growth factor (VEGF) and microvessel density (MVD) were examined by immunohistochemistry, while VEGF mRNA was determined by real-time PCR in tumor tissue. Results: The expression of MVD and VEGF decreased gradually as the concentration of GPC increased.There was a significant positive correlation between MVD and VEGF. Conclusions: These results suggest that GPC restrains the growth of tumor, possibly by inhibiting tumour angiogenesis.

Anticancer Drugs at Low Concentrations Upregulate the Activity of Natural Killer Cell

  • Hyeokjin Kwon;Myeongguk Jeong;Yeeun Kim;Go-Eun Choi
    • Biomedical Science Letters
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    • v.29 no.3
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    • pp.178-183
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    • 2023
  • Natural killer (NK) cells are innate cytotoxic lymphoid cells that actively prevent neoplastic development, growth, and metastatic dissemination in a process called cancer immunosurveillance. Regulation of the cytotoxic activity of NK cells relies on integrated interactions between inhibitory receptors and numerous activating receptors that act in tandem to eliminate tumor cells efficiently. Conventional chemotherapy is designed to produce an anti-proliferative or cytotoxic effect on early tumor cell division. Therapies designed to kill cancer cells and simultaneously maintain host anti-tumor immunity are attractive strategies for controlling tumor growth. Depending on the drug and dose used, several chemotherapeutic agents cause DNA damage and cancer cell death through apoptosis, immunogenic cell death, or other forms of non-killing (i.e., mitotic catastrophe, senescence, autophagy). Among stress-induced immunostimulatory proteins, changes in the expression levels of NK cell activating and inhibitory ligands and tumor cell death receptors play an important role in the detection and elimination by innate immune effectors including NK cells. Therefore, we will address how these cytotoxic lymphocytes sense and respond to high and low concentrations of drug-induced stress to the drug cisplatin, among the various types of drugs that contribute to their anticancer activity.

Combined EGFR and c-Src Antisense Oligodeoxynucleotides Encapsulated with PAMAM Denderimers Inhibit HT-29 Colon Cancer Cell Proliferation

  • Nourazarian, Ali Reza;Najar, Ahmad Gholamhoseinian;Farajnia, Safar;Khosroushahi, Ahmad Yari;Pashaei-Asl, Roghiyeh;Omidi, Yadollah
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4751-4756
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    • 2012
  • Colon cancer continues to be one of the most common cancers, and the importance and necessity of new therapies needs to be stressed. The most important proto-oncogen factors for colon cancer appear to be epidermal growth factor receptor, EGFR, and c-Src with high expression and activity leading to tumor growth and ultimately to colon cancer progression. Application of c-Src and EGFR antisense agents simultaneously should theoretically therefore have major benefit. In the present study, anti-EGFR and c-Src specific antisense oligodeoxynucleotides were combined in a formulation using PAMAM dendrimers as a carrier. Nano drug entry into cells was confirmed by flow cytometry and fluorescence microscopy imaging and real time PCR showed gene expression of c-Src and EGFR, as well as downstream STAT5 and MAPK-1 with the tumor suppressor gene P53 to all be downregulated. EGFR and c-Src protein expression was also reduced when assessed by western blotting techniques. The effect of the antisense oligonucleotide on HT29 cell proliferation was determined by MTT assay, reduction beijng observed after 48 hours. In summary, nano-drug, anti-EGFR and c-Src specific antisense oligodeoxynucleotides were effectively transferred into HT-29 cells and inhibited gene expression in target cells. Based on the results of this study it appears that the use of antisense EGFR and c-Src simultaneously might have a significant effect on colon cancer growth by down regulation of EGFR and its downstream genes.

Selenium and Vitamin E for Prostate Cancer - Justifications for the SELECT Study

  • Ramamoorthy, Venkataraghavan;Rubens, Muni;Saxena, Anshul;Shehadeh, Nancy
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.2619-2627
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    • 2015
  • There are several studies that relate oxidative damage as possible mechanism for many cancers. Many studies have also shown that anti-oxidants like selenium and vitamin E decrease the risk for prostate cancer. The main objective of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) study was to look for the benefits of selenium and vitamin E supplementation on prostate cancer. The study had a large sample size, stringent experimental conditions, very long duration, standardized laboratories for biochemical analyses and other factors that contribute to high external validity. The SELECT study failed to show any significant risk reduction for prostate cancers ascribable to selenium and vitamin E supplementations. Because of these conflicting results, many researchers argue about the methods used, supplementations administered (selenium and vitamin E) and indicators used for assessing levels of supplementations. We reviewed many epidemiological studies, clinical trials, and pre-clinical studies. With corroborative evidences we justify that SELECT study has a sound methodology and rationale. In lieu of the contrary results of the select study, researchers should focus on the probable mechanisms for these contrary findings and continue their search for newer and effective agents for prevention of prostate cancer.

[Retracted]Anti-inflammatory activities of octapeptides derived from tertomotide ([논문철회]Tertomotide 유래 옥타펩타이드의 항염증 활성)

  • Lee, Hyosung
    • Journal of Digital Convergence
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    • v.20 no.2
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    • pp.311-316
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    • 2022
  • Tertomotide is a peptide fragment of hTert and developed as a vaccine targeting cancer. It has been reportedly known to ameliorate inflammatory symptoms in clinical tests and in animal studies. However, the therapeutic potential of tertomotide is not supposed to be comparable to conventional anti-inflammatory agents due to low druglikeness In order to treat inflammations present in varous lesion, the structure of tertomotide is required to be modified. In this context, 12 octapeptides were designed based on tertomotide and screened for the anti-inflammatory activity in activated monocyte by measuring TNF-α secretion. As a result, some octapeptides has been exerted anti-inflammatory activity, comparable to or better than tertomotide and estradiol, known anti-inflammatory agents. This result is supposed to be helpful for developing therapeutic purpose exploiting other tertomotide-derived peptides and would be an example for designing novel drug based on active biomolecules with undesirable structure by convergence study of biology and computer-aided medicinal chemistry.

Salvage Therapy of Gemcitabine Plus Endostar Significantly Improves Progression-free Survival (PFS) with Platinum-resistant Recurrent Epithelial Ovarian Cancer

  • Su, An;Zhang, Jing;Pan, Zhan-He;Zhou, Qi-Ming;Lv, Xia
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.3
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    • pp.1841-1846
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    • 2013
  • Anti-angiogenic agents have played crucial roles in the treatment of ovarian cancer in recent years, but potential benefits of endostatin have been largely unexplored. The present retrospective study evaluated its efficacy and toxicity with two cohorts of patients with platinum-resistant recurrent ovarian cancer. One cohort received gemcitabine plus endostar (rh-endostatin), and the second cohort received gemcitabine regimen alone, with totals of 31 and 27 patients, respectively. The main endpoints were disease control rate (DCR), PFS, overall survival (OS) and safety. There were statistically significant differences in DCR (70.9% vs. 40.7%; P = 0.02) and PFS (6.3 months vs. 3.2 months, P = 0.001) between the two cohorts. Though the endostar cohort also improved median OS by 2.1 months, there was no statistically significant difference compared with gemcitabine alone cohort in this case (12.5 months vs. 10.4 months, P = 0.201). Treatment was well tolerated for most patients, and toxicity of endostar was negligible. Gemcitabine plus endostar significantly improved the prognosis in patients with platinum-resistant recurrent ovarian cancer, especially in those with malignant effusion. The endostar-containing regimen is recommended in this setting.

Anti-cancer Activity of the Leave Extracts of Rodgersia podophylla through β-catenin Proteasomal Degradation in Human Cancer Cells

  • Kim, Jeong Dong;Park, Su Bin;Kim, Ha Na;Jeong, Jin Boo
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2019.10a
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    • pp.68-68
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    • 2019
  • In this study, we evaluated the effect of Rodgersia podophylla leave extracts (RPL) on ${\beta}$-catenin level in human cancer cells. RPL dose-dependently inhibited cell proliferation in SW480, A549, MDA-MB-231, PC-3 and AsPC-1 cells. RPL dramatically decreased ${\beta}$-catenin protein level in all cancer cells. However, decreased level of ${\beta}$-catenin mRNA expression was observed in A549 and AsPC-1 cells. In addition, RPL dramatically attenuated cyclin D1 mRNA expression in all cancer cells. MG132 decreased the downregulation of ${\beta}$-catenin protein level induced by RPL in all cancer cells, while RPL-induced downregulation of ${\beta}$-catenin was inhibited by the inhibition of $GSK-3{\beta}$ by LiCl in MDA-MB-231 cells. RPL phosphorylated ${\beta}$-catenin and $GSK-3{\beta}$. In addition, the inhibition of $GSK-3{\beta}$ by LiCl attenuated RPL-induced ${\beta}$-catenin phosphorylation. Based on these findings, RPL may be a potential candidate for the development of chemopreventive or therapeutic agents for human cancer.

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Hexane and Chloroform Fractions of Laetiporus sulphrueus var. miniatus Inhibit Thrombin-treated Matrix Metalloproteinase-2/9 Expression in Human Oral Squamous Carcinoma YD-10B Cells

  • Kim, Eun-Jung;Yoo, Kwan-Hee;Kim, Yang-Sup;Seok, Soon-Ja;Kim, Jun-Ho
    • The Korean Journal of Mycology
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    • v.45 no.3
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    • pp.175-187
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    • 2017
  • Laetiporus sulphrueus var. miniatus is widely distributed worldwide, and has commonly been used as a medicinal mushroom. In the present study, we investigated the effects of water extract and solvent fractions from the Laetiporus miniatus as possible antioxidant, anti-thrombin and anti-invasive agents against phorbol 12-myristate 13-acetate (PMA)- or thrombin-induced matrix metalloproteinase-2 (MMP-2) and MMP-9 activities. Samples were fractionated into n-hexane, $CHCl_3$, ethyl acetate, n-butanol, and water fractions, and individually analysed. The water fraction had the highest extraction yield at 34.90% (w/w), while the n-butanol fraction demonstrated the highest anti-oxidative activity at 81.44%. In the thrombin inhibitory activity test, the water fraction exhibited the highest activity at 94.64%. Even at the concentration of $40{\mu}g/mL$, evaluation of anti-proliferating activity in YD-10B cells did not reveal any cytotoxic effects. Although MMP-9 expression in YD-10B cells increased after the addition of PMA and thrombin, MMP-2 did not. Additionally, MMP-2/-9 levels in PMA-treated YD-10B cells (i.e., both mRNA expression and protein activation) were highly inhibited in the hexane and chloroform fractions. Compared with MMP-2 levels, MMP-9 mRNA expression and proteolytic activity were inhibited to a greater extent by the hexane and chloroform fractions in thrombin-treated YD-10B cells. Taken together, these results support that thrombin induces tumor invasion through MMP-2/9 and suggest that the L. miniatus may act as an effective functional food, conferring anti-oxidative, anti-thrombotic and anti-cancer activities.

Inhibitory Activity of Drug-metabolizing Enzyme CYP3A4 of Zanthoxylum Peel (산초의 약물대사효소 CYP3A4 저해 활성)

  • Cha, Bae Cheon
    • Korean Journal of Pharmacognosy
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    • v.50 no.3
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    • pp.159-164
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    • 2019
  • Zanthoxylum Peel is widely used as a common spice for a variety of foods. In the orient, it has also been used as traditional agents for treating diseases such as indigestion. Recently, Zanthoxylum Peel has been reported to have anti-cancer activity, anti-microbial activity, and anti-inflammatory activity. Chemical components are known sanshool compounds and xanthoxylin. In this study, we were carried out to investigate the constituents of inhibiting a drug metabolizing enzyme CYP3A4 from Zanthoxylum Peel. CYP3A4 is known as an enzyme involved in drug metabolism as monooxygenase containing the heme. As a result of experiment, we found that bergapten ($IC_{50}=18.21{\mu}M$) and quercetin ($IC_{50}=17.27{\mu}M$) isolated from EtOAc extract of Zanthoxylum Peel showed remarkable CYP3A4-inhibiting activities. Structures of the isolated active compounds were established by chemical and spectroscopic means.

Low-Dose Off-Label Use of Phentermine/Topiramate in the Individual with Morbid Obesity and Postoperative Hypothyroidism (수술 후 갑상선기능저하가 동반된 고도비만환자의 펜터민염산염/토피라메이트의 저용량 오프라벨 사용)

  • Park, Jung Ha
    • Archives of Obesity and Metabolism
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    • v.1 no.1
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    • pp.43-45
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    • 2022
  • Intensive lifestyle modifications and anti-obesity medications are essential for obesity treatment. Antiobesity medications should be selected according to the patient's comorbidities, symptoms, and preferences. This case report describes the treatment of a morbidly obese patient with a history of depression, who complained of tingling and numbness after total thyroidectomy for papillary thyroid cancer. Very low-dose controlled-release phentermine/topiramate was prescribed and intensive lifestyle modifications were encouraged. As a result, the patient effectively lost weight and reached a near-normal weight without adverse drug effects. This implies that even an off-label anti-obesity medication low dose may be better for some patients, and the most important factor in obesity treatment is patient-tailored treatment.