• Title/Summary/Keyword: toxicity reduction efficacy

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Comparative Analysis of the Efficacy and Safety of Oxaliplatin Plus 5-Fluorouracil/Leucovorin (Modified FOLFOX6) with Advanced Gastric Cancer Patients having a Good or Poor Performance Status

  • Hacibekiroglu, Ilhan;Kodaz, Hilmi;Erdogan, Bulent;Turkmen, Esma;Esenkaya, Asim;Uzunoglu, Sernaz;Cicin, Irfan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2355-2359
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    • 2015
  • Background: Combination chemotherapy of 5 fluorouracil (5-FU) and leucovorin (LV) with oxaliplatin, mainly FOLFOX regimens, has shown considerable antitumor activity and a tolerable toxicity profile in gastric cancer. The goal of this study was to retrospectively compare the efficacy and toxicity of modified FOLFOX-6 (mFOLFOX6) regimen in advanced gastric cancer (AGC) patients with good and poor performance status (PS). Materials and Methods: AGC patients receiving the mFOLFOX6 regimen including oxaliplatin $85mg/m^2$, bolus of 5-FU $400mg/m^2$ and LV $400mg/m^2$ on the first day, followed by $2400mg/m^2$ of 5- FU as a continious infusion over 46 hour for first-line treatment were eligible for the study. Results: A total 58 patients with a median age of 59.5 (32-81) were included. The median follow up of the study was 9.2 months. Thirty patients (51.7%) with an ECOG PS 0-1 were assigned to the good PS arm, while 28 patients (48.3%) with ECOG PS 2 were in the poor PS arm. Overall response rates were 36.6 and 28.8%, respectively (p=0.91). Median PFS was 6.7 and 6.3 months in good PS and poor PS arms (p=0.50) and median OS was 9.6 and 10.4 months (p=0.55). As compared with good PS arm, poor PS arm was associated with more grade 3-4 neutropenia and anemia. Dose reduction and dose delays were also significantly higher. Conclusions: In this study, mFOLFOX6 was similarly effective in both arms. Although hematologic toxicity was significantly higher in patients with poor PS, it remained manageable. Our results suggest that this regimen may be an effective treatment option for AGC patients with poor PS.

Two-Week Combination Chemotherapy with Gemcitabine, High-Dose Folinic Acid and 5 Fluorouracil (GEMFUFOL) as First-Line Treatment of Metastatic Biliary Tract Cancers

  • Unal, Olcun Umit;Oztop, Ilhan;Unek, Ilkay Tugba;Yilmaz, Ahmet Ugur
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5263-5267
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    • 2013
  • Background: The aim of this study was to evaluate the efficacy and tolerability of a gemcitabine, 5-fluorouracil and leucovorin (GEMFUFOL) chemotherapy regimen as first line treatment of metastatic biliary tract cancer. Materials and Methods: All patients received folinic acid $400mg/m^2$ on day 1, 5-fluorouracil bolus $400mg/m^2$ on day 1, IV infusion of 5-fluorouracil $2400mg/m^2$ over 46 hours, and gemcitabine $1250mg/m^2$ on day 1. Results: A total of 29 patients with metastatic biliary tract cancer received GEMFUFOL regimen as the firstline treatment. The mean follow-up was 22.1 months (95%CI, 12.5-31.8). One patient (3.4%) achieved complete response, 5 (17.2%) had partial response, and 4 (13.8%) had stable disease. The median progression-free survival was 3.3 months (95%CI, 2.9-3.7), and the median overall survival was 8.8 months (95%CI, 3.5-14). The 1-year and 2-year survival rates were 58.6% and 30%, respectively. Grade 3 and 4 toxicity included neutropenia in 4 patients (13.7%), thrombocytopenia in 2 (6.8%), anemia2 (6.8%), and alopecia in 1 (3.4%). Two patients (6.8%) developed febrile neutropenia. A dose reduction was achieved in 8 patients (27.6%) while 5 patients had extended-interval dosage (17.2%) for toxicity. Conclusions: The GEMFUFOL chemotherapy regimen was generally efficacious and tolerable as a first-line treatment of metastatic biliary tract cancer.

Anti-Tuberculosis Activity of Pediococcus acidilactici Isolated from Young Radish Kimchi against Mycobacterium tuberculosis

  • Yoon, Youjin;Seo, Hoonhee;Kim, Sukyung;Lee, Youngkyoung;Rahim, MD Abdur;Lee, Saebim;Song, Ho-Yeon
    • Journal of Microbiology and Biotechnology
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    • v.31 no.12
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    • pp.1632-1642
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    • 2021
  • Tuberculosis is a highly contagious disease caused by Mycobacterium tuberculosis. It affects about 10 million people each year and is still one of the leading causes of death worldwide. About 2 to 3 billion people (equivalent to 1 in 3 people in the world) are infected with latent tuberculosis. Moreover, as the number of multidrug-resistant, extensively drug-resistant, and totally drug-resistant strains of M. tuberculosis continues to increase, there is an urgent need to develop new anti-tuberculosis drugs that are different from existing drugs to combat antibiotic-resistant M. tuberculosis. Against this background, we aimed to develop new anti-tuberculosis drugs using probiotics. Here, we report the anti-tuberculosis effect of Pediococcus acidilactici PMC202 isolated from young radish kimchi, a traditional Korean fermented food. Under coculture conditions, PMC202 inhibited the growth of M. tuberculosis. In addition, PMC202 inhibited the growth of drug-sensitive and -resistant M. tuberculosis- infected macrophages at a concentration that did not show cytotoxicity and showed a synergistic effect with isoniazid. In a 2-week, repeated oral administration toxicity study using mice, PMC202 did not cause weight change or specific clinical symptoms. Furthermore, the results of 16S rRNA-based metagenomics analysis confirmed that dysbiosis was not induced in bronchoalveolar lavage fluid after oral administration of PMC202. The anti-tuberculosis effect of PMC202 was found to be related to the reduction of nitric oxide. Our findings indicate that PMC202 could be used as an anti-tuberculosis drug candidate with the potential to replace current chemical-based drugs. However, more extensive toxicity, mechanism of action, and animal efficacy studies with clinical trials are needed.

Anticancer effect of metformin alone and in combination with 2-deoxy-D-glucose on mouse T cell lymphoma EL4 cells (마우스 T 세포 림프종 EL4 세포에 대한 metformin 단독 및 2-deoxy-D-glucose와 병용의 항암효과 )

  • Si-Yeon Kim;Hong-Gu Joo
    • Korean Journal of Veterinary Research
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    • v.63 no.3
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    • pp.30.1-30.8
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    • 2023
  • Metformin is a treatment used widely for non-insulin-dependent diabetes mellitus with few side effects and acts by inhibiting hepatic gluconeogenesis and glucose absorption from the gastrointestinal tract. Lymphoma is one of the most common hematological malignancies in dogs. Chemotherapy is used mainly on lymphoma, but further research on developing anticancer drugs for lymphoma is needed because of its severe side effects. This study examined the anticancer effects of metformin alone and in combination with 2-deoxy-D-glucose (2-DG), a glucose analog, on EL4 cells (mouse T cell lymphoma). Metformin reduced the metabolic activity of EL4 cells and showed an additive effect when combined with 2-DG. In addition, cell death was confirmed using a trypan blue exclusion test, Hochest 33342/propidium iodide (PI) staining, and Annexin V/PI staining. An analysis of the cell cycle and mitochondria membrane potential (MMP) to investigate the mechanism of action showed that metformin stopped the G2/M phase of EL4 cells, and metformin + 2-DG decreased MMP. Metformin exhibited anticancer effects as a G2/M phase arrest mechanism in EL4 cells and showed additive effects when combined with 2-DG via MMP reduction. Unlike cytotoxic chemotherapeutic anticancer drugs, metformin and 2-DG are related to cellular glucose metabolism and have little toxicity. Therefore, metformin and 2-DG can be an alternative to reduce the toxicity caused by chemotherapeutic anticancer drugs. Nevertheless, research is needed to verify the in vivo efficacy of metformin and 2-DG before they can be used in lymphoma treatments.

Efficacy of Curcumin in the Modulation of Anxiety Provoked by Sulfite, a Food Preservative, in Rats

  • Noorafshan, Ali;Vafabin, Masoud;Karbalay-Doust, Saied;Asadi-Golshan, Reza
    • Preventive Nutrition and Food Science
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    • v.22 no.2
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    • pp.144-148
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    • 2017
  • Sulfites are used as food preservatives and excessive sulfite might disturb the body systems including the brain. Curcumin shows protective effects on the nervous system toxicity. The present study aimed to evaluate the protective role of curcumin in sulfite-induced anxiety in rats. Male rats were divided into five groups. The rats in groups I to V received distilled water (vehicle of sulfite, 1 mL/d), olive oil (vehicle of curcumin, 1 mL/d), curcumin (100 mg/kg/d), sulfite (25 mg/kg/d), and sulfite+curcumin, respectively, by daily gastric gavage for 8 weeks. At the end of 8 weeks the rats were tested in the elevated plus-maze for anxiety. The results showed that concomitant treatment of curcumin during sulfite consumption prevented the reduction of the time spent in the open arm and entrance to the open arm (the indexes of anxiety). Besides, an increase was found in motor activity of the rats in the sulfite+curcumin group compared to the sulfite-treated animals. Exposure of sulfite in rats can induce anxiety, and curcumin can act as an anti-anxiety agent.

Evaluation of Whitening Activity and Wrinkle Inhibitory Effect of Ethanol Extracts of Nelumbinis Rhizomatis Nodus (우절 에탄올추출물의 미백활성능과 주름저해 효능평가)

  • Jang, Young-Ah;Yeom, Bo-Seul;Kim, Se-Gie;Lee, Jin-Tae
    • Journal of Life Science
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    • v.29 no.11
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    • pp.1192-1199
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    • 2019
  • The intention of this study was to confirm the possible use of an ethanol extracts of Nelumbinis Rhizomatis Nodus (NRN) as a cosmetic material. To this end, we extracted NRN with 70% ethanol and performed biological activity evaluation of whitening efficacy and wrinkle reduction. We performed cellular tyrosinase inhibition and melanin contents assay to check the whitening activity of NRN and carried out a toxicity evaluation of NRN via an MTT assay and the amounts of associated proteins that affect melanin production in a melanoma cell line (B16F10). And collagenase inhibitory assay was performed for the evaluation of anti-wrinkle of samples. In addition, a toxicity evaluation using an MTT assay and matrix metalloprotease (MMP-1) and procollagen synthesis inhibition by NRN were evaluated in a fibroblast cell line (CCD-986sk). Western blot results for the whitening activity evaluation revealed that the levels of two proteins related to melanin production, tyrosinase-related protein-1 (TRP-1) and tyrosinase-related protein-2 (TRP-2), were decreased in a dose-dependent manner. Moreover, collagenase inhibition activity at a concentration of $500{\mu}g/ml$ NRN by measuring epigallocatechin-3-gallate (EGCG) was increased by more than 80% compared to the control group. Meanwhile, procollagen synthesis was reduced by 68.8% in the UVB-induced CCD- 986sk cells group whereas collagen synthesis recovered by 80.2% with $25{\mu}g/ml$ NRN. The MMP-1 expression rate showed 20.2% reduction at $25{\mu}g/ml$. The results of the experiments verified the whitening and wrinkle suppression effects of NRN and confirmed that it could be used as a safe natural cosmetic material in the future.

Palmijihwang-tang Alleviates Cisplatin-induced Nephrotoxicity through Inhibiting ROS Production and p53 Activation (팔미지황탕(八味地黃湯)의 ROS 생성 및 p53 활성 조절을 통한 시스플라틴 신장독성 완화효과)

  • Ju, Sung-Min;Park, Seo-Hee;Chong, Myong-Soo;Jeon, Byung-Hun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.34 no.4
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    • pp.170-176
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    • 2020
  • Palmijihwang-tang is an herbal formula frequently used to treat many symptoms, such as lumbago, pollakiuria, cold hands and feet, nephritis, sterilitas virilis, and prostatic disorders. The aim of this study was to investigate the effects of Palmijihwang-tang on cisplatin-induced nephrotoxicity in rat kidney proximal tubular NRK-52E cells. NRK-52E cells were treated with Palmijihwang-tang in absence or presence of 30 µM cisplatin for 12 or 24 h. Palmijihwang-tang at concentrations of 50-800 ㎍/ml did not change the cell viability in NRK-52E cells, and showed no significant toxicity. Palmijihwang-tang at concentrations of 400 and 800 ㎍/ml significantly increased the cell viability and reduced apoptotic cells in NRK-52E cells exposed to cisplatin. Also, Palmijihwang-tang markedly inhibited cisplatin-induced caspase-3 activation, PARP cleavage, ROS production and p53 activation in NRK-52E cells. Furthermore, Palmijihwang-tang did not interfere with the antitumor activity of cisplatin in AGS and A549 cancer cells. Particularly, Palmijihwang-tang enhanced antitumor activity of cisplatin in A549 cells. Taken together, these results suggest that Palmijihwang-tang ameliorated cisplatin-induced nephrotoxicity through reduction of ROS production and p53 activation, and did not interrupt antitumor efficacy of cisplatin against cancer cells.

Impact of peripheral blood mononuclear cells preconditioned by activated platelet supernatant in managing gastric mucosal damage induced by zinc oxide nanoparticles in rats

  • Darwish Badran;Ayman El-Baz El-Agroudy;Amira Adly Kassab;Khaled Saad El-Bayoumi;Zienab Helmy Eldken;Noha Ramadan Mohammed Elswaidy
    • Anatomy and Cell Biology
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    • v.57 no.1
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    • pp.105-118
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    • 2024
  • The world has witnessed tremendous advancements in nano-base applications. Zinc oxide nanoparticles (ZON) are widely used in food industry and medicine. Although their application is of important value, they may cause toxicity to body tissues. Peripheral blood mononuclear cells (PBMCs) proved its efficacy in tissue regeneration especially when it is preconditioned by activated platelet supernatant (APS). The aim of this study is to evaluate the effect of ZON on the gastric mucosa and the therapeutic role of the PBMCs preconditioned by APS in rats. Ten rats were donors and fifty rats were recipients. The recipients were divided into; control group, ZON group (10 mg/kg/day orally for five days) and preconditioned PBMCs group (1×107 once intravenously 24 hours after ZON). Gastric specimens were processed for histological, immunohistochemical, biochemical and quantitative real-time polymerase chain reaction studies. ZON group showed marked structural changes in the gastric mucosa. There was desquamation or deep ulceration of the epithelium. Cytoplasmic vacuoles and pyknotic nuclei were in glandular cells. Reduced proliferating cell nuclear antigen and increased tumor necrosis factor-α were in epithelial cells. There were significant elevation in malondialdahyde and reduction in glutathione, superoxide dismutase, and catalase. Enhancement in mRNA expression of nuclear factor kappa-B and cyclooxygenase-2 was detected. The preconditioned PBMCs group showed significant improvement of all parameters. So, ZON had cytotoxic effects on the gastric mucosa and the preconditioned PBMCs had a therapeutic effect on gastric mucosal damage after ZON.

Gomisin A Inhibits Tumor Growth and Metastasis through Suppression of Angiogenesis (Gomisin A의 신혈관형성 저해를 통한 종양 성장 및 전이 억제 효과)

  • Kim, Do-Yoon;Yu, Ho-Jin;Yoon, Mi-So;Park, Joo-Hoon;Jang, Sang-Hee;Lee, Hwan-Myung
    • Journal of Life Science
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    • v.22 no.9
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    • pp.1224-1230
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    • 2012
  • Cancer chemotherapy drugs command a large share of the market, and the development of new therapeutics with high efficacy and specificity is an active area of study. Recently, the development of cancer therapeutics from natural products targeting angiogenesis has drawn attention due to conventional chemotherapeutics showing serious side effects and resistance in cancer cells. In this study, we investigated the pharmacological efficacy of Gomisin A, an active ingredient of Schizandra chinensis baillon, on tumor growth and metastasis. Administration of Gomisin A at 10 and 100 ${\mu}g/ml$ reduced tumor growth in vivo by $80.5{\pm}8.1%$ and $96.2{\pm}2%$, respectively, compared with positive tumor controls. Treatment of Gomisin A in normal and various tumor cell lines did not exert significant toxicity. Mice treated with Gomisin A at a concentration of 10 and 100 ${\mu}g$/head showed a significant reduction in tumor-induced angiogenesis of $151{\pm}16.9%$ and $98.5{\pm}29.5%$, respectively. Furthermore, tumor metastasis analysis revealed that the administration of Gomisin A at a concentration of 10 and 100 ${\mu}g$/head inhibited tumor metastasis by $13.5{\pm}8.56%$ and $58.3{\pm}9.12%$, respectively. In addition, Gomisin A significantly decreased cell adhesion of the B16BL6 cells to the extracellular matrix. These results demonstrate that Gomisin A inhibits tumor growth via suppression of angiogenesis and tumor metastasis inhibition, without cellular toxicity. The pharmacological efficacy of Gomisin A suggests that it may be a potential candidate for the development of cancer drugs.

Antioxidant Effect of Arthrospira platensis Extract and Effect on UVB-induced Free Radical Production (Arthrospira platensis 추출물의 항산화 및 UVB에 의해 유도된 활성산소 생성에 미치는 영향)

  • Kim, Min Seung;Yang, Jae-Chan;Kim, Bo-Ae
    • Journal of the Korean Applied Science and Technology
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    • v.37 no.2
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    • pp.153-161
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    • 2020
  • Arthrospira platensis is the oldest marine microalgae on the planet, is said to contain most of the nutrients needed by the human body. It's components are reported to contain a large amount of various substances such as phycocyanin, chlorophyll and β-carotene, and are known to have an aging and whitening effect. In this study, UVB-induced reactive oxygen species reduction efficacy and antioxidant activity of spirulina purified water extract were investigated. effect was confirmed by measuring DPPH radical scavenging activity, FRAP reducing power and ABTS+ radical scavenging activity of 0.05, 0.10, 0.50 1.0 mg/mL of spirulina purified water extract. The coagulation rate, hatching rate and heart rate toxicity were measured by treating spirulina purified water extract with 0.05, 0.10, 0.50 mg/mL concentration using Zebrafish, an alternative experimental animal model. UVB-induced ROS measurement was treated with spirulina extract at 0.05, 0.10, 0.50 mg/mL concentration, and then stained with DCFH-DA to confirm the inhibitory effect of ROS. As a result of measuring antioxidant effect, DPPH, FRAP and ABTS+ showed concentration-dependent antioxidant effects in comparison with ascorbic acid. and measuring the coagulation rate, hatching rate, and heart rate using Zebrafish, an alternative experimental animal, it was confirmed that there was no toxicity in 0.05 and 0.10 mg/mL except 0.5 mg/mL compared to the control group. The ROS scavenging activity of UVB-induced zebrafish showed higher ROS reduction than the positive control. The results of this study suggest that spirulina and purified water extracts are valuable for UV and skin protection cosmetics.