Yildirim, Fatma;Baha, Ayse;Yurdakul, Ahmet Selim;Ozturk, Can
Asian Pacific Journal of Cancer Prevention
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v.16
no.17
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pp.7859-7863
/
2015
Purpose: To compare the efficacy and toxicity of gemcitabine versus docetaxel in a second-line setting of nonsmall cell lung cancer (NSCLC) patients previously treated with platin-based combination chemotherapy. Materials and Methods: We retrospectively evaluated the medical records of 57 patients treated with single agent gemcitabine or docetaxel in second-line setting of advanced NSCLC who received one prior platinum-based therapy. Results: The mean age was $56.7{\pm}8.39$ years with 55 (96.5%) males and two (3.5%) females. Forty of them received docetaxel and 17 gemcitabine. The mean number of chemotherapy cycles was $6.8{\pm}4.0$ in the gemcitabine group, while it was $4.6{\pm}3.0$ in the docetaxel group. Overall response rates were 8% and 12% (P=0.02) for gemcitabine and docetaxel, respectively. The median survival time was 22 versus 21 months for gemcitabine and docetaxel, respectively. The median times to progression were 8 and 5 months. There was no difference between the two groups in terms of incidence of adverse affects (40% vs 47.1%). All of the hematological side effects were grade 1/2. No major toxicity was encountered necessitating stopping the drug for either group. Conclusions: Treatment with gemcitabine demonstrated clinically equivalent efficacy with a significantly improved safety profile compared with those receiving docetaxel in the second-line setting for advanced NSCLC in this study. Based on these results, treatment with gemcitabine should be considered a standard treatment option for second-line NSCLC.
Al Mahmud, Jubayer;Hasanuzzaman, Mirza;Nahar, Kamrun;Rahman, Anisur;Hossain, Md. Shahadat;Fujita, Masayuki
Proceedings of the Korean Society of Crop Science Conference
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2017.06a
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pp.235-235
/
2017
Chromium (Cr) toxicity is hazardous to the seed germination, growth, and development of plants. ${\gamma}$-Aminobutyric acid (GABA) is a non-protein amino acid and is involved in stress tolerance in plants. To investigate the effects of GABA in alleviating Cr toxicity, we treated eight-d-old mustard (Brassica juncea L.) seedlings with Cr (0.15 mM and 0.3 mM $K_2CrO_4$, 5 days) alone and in combination with GABA ($125{\mu}M$) in a semi-hydroponic medium. The roots and shoots of the seedlings accumulated Cr in a dose-dependent manner, which led to an increase in oxidative damage [lipid peroxidation; hydrogen peroxide ($H_2O_2$) content; superoxide ($O{_2}^{{\cdot}-}$) generation; lipoxygenase (LOX) activity], MG content, and disrupted antioxidant defense and glyoxalase systems. Chromium stress also reduced growth, leaf relative water content (RWC), and chlorophyll (chl) content but increased phytochelatin (PC) and proline (Pro) content. Furthermore, supplementing the Cr-treated seedlings with GABA reduced Cr uptake and upregulated the non-enzymatic antioxidants (ascorbate, AsA; glutathione, GSH) and the activities of the enzymatic antioxidants including ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), glutathione reductase (GR), glutathione peroxidase (GPX), superoxide dismutase (SOD), catalase (CAT), glyoxalase I (Gly I), and glyoxalase II (Gly II), and finally reduced oxidative damage. Adding GABA also increased leaf RWC and chl content, decreased Pro and PC content, and restored plant growth. These findings shed light on the effect of GABA in improving the physiological mechanisms of mustard seedlings in response to Cr stress.
Background: Lung cancer is the most common cancer in males worldwide. The principal mode of treatment in the early stage of non-small cell lung cancer (NSCLC) is surgery. However, five-year survival is only about 15% for all stages. The aim is to investigate the effect of daily low dose cisplatin concurrently with radiation therapy in advanced NSCLC patients with poor performance status. Materials and Methods: Ten patients diagnosed as inoperable Stage IIIB NSCLC with comorbid disease were assessed retrospectively in Bezmialem Vakif University, Faculty of Medicine, Department of Radiation Oncology, between 2011 to 2013. ECOG performance status was between 3 and 4. Cisplatin was administered at $6mg/m^2$ daily, for 5 days a week concurrently with radiotherapy using 160-200 cGy daily fractions, 54 Gy being the lowest and 63 Gy being the highest dose. Results: Complete response at the primary tumour site was obtained in 20% patients. Grade I esophagitis was seen 70 percent of patients, and the grade II haematological toxicity rate was 20 %. Median survival time was 7 months. Conclusions: Median survival time was reasonable, despite the patients ECOG performance status of 3-4, which is similar to groups even without comorbid disorders in comparison to other published papers in the literature. Acceptable toxicity, high response rates and quality of life of patients are the other favourable features.
Lim, Jong Kwon;Seo, Hyo Jin;Kim, Eun Ok;Meydani, Mohsen;Kim, Jong Deog
Journal of Marine Bioscience and Biotechnology
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v.1
no.3
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pp.156-162
/
2006
The halophilic enterobacteria, Enterobacteria cancerogenus, was isolated from the intestines of the fusiform fish (Trachurus japonicus) to yield a protein-like material termed PLM-f74. PLM-f74 was characterized by strong inhibition ratios to angiogenesis (82.8% at the concentration of $18.5{\mu}g/mL$) and elevated antioxidative capacities with low toxicity. The PLM-f74 is a glycoprotein comprised of saccharides and amino acids. PLM-f74 inhibited non-activated U937 monocytic cell adhesion to HUVECs activated with IL-$1{\beta}$ by 78.0%, and the adherence of U937 cells treated with the PLM-f74 and stimulated with IL-$1{\beta}$ to unstimulated HUVECs decreased by 102%. When both cell types were pretreated with PLM-f74, the adhesion of U937 cells to IL-$1{\beta}$ stimulated HUVECs was completely suppressed by 121% at a concentration of 18.5 ug/mL. PLM-f74 blocked signal pathways from VEGFR2, PI3K, ${\beta}$-catenin and VE-cadherin to NF-kB based on western bolt analysis. And also inhibited IL-1-stimulated HUVEC expression of the adhesion molecules, ICAM-1 by 40%, VCAM-1 by 60%, and E-selectin by 70% at the same concentration noted above. New anti-angiogenic and anti-cell adhesion materials showing elevated antioxidative capacities and non-toxicity may be expected from these results.
The halophilic enterobacteria, Enterobacteria cancerogenus, was isolated from the intestines of the fusiform fish (Trachurus japonicus) to yield a protein-like material termed PLM-f74. PLM-f74 was characterized by strong inhibition ratios to angiogenesis (82.8% at the concentration of $18.5{\mu}g/ml$) and elevated antioxidative capacities with low toxicity. The PLM-f74 is a glycoprotein comprised of saccharides and amino acids. PLM-f74 inhibited cell adhesion that non-activated U937 monocytic cell adhesion to HUVECs activated with $IL-1{\beta}$ by 78.0%, and the adherence of U937 cells treated with the PLM-f74 and stimulated with $IL-1{\beta}$ to unstimulated HUVECs decreased by 102%. When both cell types were pretreated with PLM-f74, the adhesion of U937 cells to $IL-1{\beta}$-stimulated HUVECs was completely suppressed by 121% at a concentration of $18.5{\mu}g/ml$. PLM-f74 blocked signal pathways from VEGFR2, PI3K, ${\beta}$-catenin, and VE-cadherin to NF-kB, based on western bolt analysis. It also inhibited IL-l-stimulated HUVEC expression of the adhesion molecules, ICAM-l by 40%, VCAM-l by 60%, and E-selectin by 70% at the same concentration noted above. New anti-angiogenic and anti-cell adhesion materials showing elevated antioxidative capacities, and non-toxicity may be expected from these results.
Exposures to lead (Pb) are associated with neurological problems including psychiatric disorders and impaired learning and memory. Pb can be absorbed by iron transporters, which are up-regulated in hereditary hemochromatosis, an iron overload disorder in which increased iron deposition in various parenchymal organs promote metal-induced oxidative damage. While dysfunction in HFE (High Fe) gene is the major cause of hemochromatosis, the transport and toxicity of Pb in Hfe-related hemochromatosis are largely unknown. To elucidate the relationship between HFE gene dysfunction and Pb absorption, H67D knock-in Hfe-mutant and wild-type mice were given drinking water containing Pb 1.6 mg/ml ad libitum for 6 weeks and examined for behavioral phenotypes using the nestlet-shredding and marble-burying tests. Latency to nestlet-shredding in Pb-treated wild-type mice was prolonged compared with non-exposed wild-types (p < 0.001), whereas Pb exposure did not alter shredding latency in Hfe-mutant mice. In the marble-burying test, Hfe-mutant mice showed an increased number of marbles buried compared with wild-type mice (p = 0.002), indicating more repetitive behavior upon Hfe mutation. Importantly, Pb-exposed wild-type mice buried more marbles than non-exposed wild-types, whereas the number of marbles buried by Hfe-mutant mice did not change whether or not exposed to Pb. These results suggest that Hfe mutation could normalize Pb-induced behavioral alteration. To explore the mechanism of repetitive behavior caused by Pb, western blot analysis was conducted for proteins involved in brain dopamine metabolism. The levels of tyrosine hydroxylase and dopamine transporter increased upon Pb exposure in both genotypes, whereas Hfe-mutant mice displayed down-regulation of the dopamine transporter and dopamine D1 receptor with D2 receptor elevated. Taken together, our data support the idea that both Pb exposure and Hfe mutation increase repetitive behavior in mice and further suggest that these behavioral changes could be associated with altered dopaminergic neurotransmission, providing a therapeutic basis for psychiatric disorders caused by Pb toxicity.
Choi, Jong Hyun;Choi, Juwhan;Chung, Sang Mi;Oh, Jee Youn;Lee, Young Seok;Min, Kyung Hoon;Hur, Gyu Young;Shim, Jae Jeong;Kang, Kyung Ho;Lee, Hyun Kyung;Lee, Sung Yong
Tuberculosis and Respiratory Diseases
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v.82
no.3
/
pp.211-216
/
2019
Background: Docetaxel is one of the standard treatments for advanced non-small cell lung cancer. Docetaxel is usually administered in a 3-week schedule, but there is significant toxicity. In this phase II clinical study, we investigated the efficacy and safety of a 4-weekly schedule of docetaxel monotherapy, as first-line chemotherapy for advanced squamous cell carcinoma in elderly lung cancer patients. Methods: Patients with stage IIIB/ IV lung squamous-cell carcinoma age 70 or older, that had not undergone cytotoxic chemotherapy were enrolled. Patients received docetaxel $25mg/m^2$ on days 1, 8, and 15, every 4 weeks. Primary endpoint was the objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity profiles. Results: A total of 19 patients were enrolled. Among 19 patients, 17 were for evaluated efficacy and safety. In the intent-to-treat population, ORR and disease control rate (DCR) were 11.8% and 47.1%, respectively. In the response evaluable population, ORR was 16.7% and DCR was 66.7%. Median PFS and OS were 3.1 months and 3.3 months, respectively. There were three adverse grade 3/4 events. Grade 1 neutropenia was reported in one patient. Conclusion: Our data failed to demonstrate efficacy of a 4-weekly docetaxel regimen, in elderly patients with a poor performance status. However, incidence of side effects, including neutropenia, was lower than with a 3-week docetaxel regimen, as previously reported.
Water-dispersible ZnS:Mn nanocrystals were synthesized by capping the surface of the nanocrystals with conventional aminoacids ligands: serine and threonine. The aminoacids capped ZnS:Mn nanocrystal powders were characterized by XRD, HR-TEM, EDXS, ICP-AES and FT-IR spectroscopy. The optical properties were also measured by UV/Vis and solution photoluminescence (PL) spectroscopies in aqueous solvents. The solution PL spectra showed broad emission peaks around 600 nm with PL efficiencies of 9.7% (ZnS:Mn-Ser) and 15.4% (ZnS:Mn-Thr) respectively. The measured particle sizes for the aminoacid capped ZnS:Mn nanocrystals by HR-TEM images were about 3.0-4.0 nm, which were also supported by Debye-Scherrer calculations. In addition, cytotoxic effects of four aminoacids capped ZnS:Mn nanocrsystals over the growth of wild type E. coli were investigated. Although toxicity in the form of growth inhibition was observed with all the aminoacids capped ZnS:Mn nanocrystals at higher dose (1 mg/mL), ZnS:Mn-Met and ZnS:Mn-Thr appeared non-toxic at doses less than 100 ${\mu}g$/mL. Low biological toxicities were seen at doses less than 10 ${\mu}g$/ mL for all nanocrystals.
Objectives: This study evaluated the single-dose toxicity of Saeng Maek San (SMS) in rats. Methods: All experiments were conducted at Biotoxtech (Chungwon, Korea), an institute authorized to perform non-clinical studies under the regulations of Good Laboratory Practice (GLP). A single-dose intravenous toxicity study was carried out on 40 6-week-old Sprague-Daley rats. The animals were randomly divided into the following four groups of ten animals each: Group 1 (G1) was the control group, with each animal receiving an intravenous injection of 1.0 mL of saline, and Groups 2, 3 and 4 (G2, G3 and G4) were the experimental groups, with the animals in the groups receiving an injection of 0.1, 0.5 and 1.0 mL of SMS, respectively. Mortality, clinical signs, body-weight changes and gross pathological findings were observed for 14 days following a single administration of SMS or saline. Organ weights, clinical chemistry and hematology were analyzed at 14 days. This study was conducted with the approval of the Institutional Animal Ethics Committee. Results: No deaths occurred in any of the four groups, indicating that the lethal dose of SMS in rats is greater than 1.0 mL/animal. Some changes in weights of male rats between the control group and the experimental groups were observed, but no significant changes in the weights of female rats were noted. To identify abnormalities in organs and tissues, we stained representative sections of each specified organ with hematoxylin and eosin for examination with a light microscope. No significant abnormalities were observed in any of the organs or tissues. Conclusion: The results suggest that intravenous injection of SMS is a safe method of treatment.
Objectives: This study was performed to analyze single dose toxicity and the lethal dose of Scolopendrid Pharmacopuncture in rats. Methods: All experiments were conducted at the Korea Testing & Research Institute (KTR), an institution authorized to perform non-clinical studies, under the regulations of Good Laboratory Practice (GLP). Sprague-Dawley rats were chosen for the pilot study. Doses of Scolopendrid pharmacopuncture, 0.1, 0.5, and 1.0 mL, were administered to the experimental group, and 1.0 mL doses of normal saline solution were administered to the control group. This study was conducted under the approval of the Institutional Animal Ethic Committee. Results: No deaths or abnormalities occurred in any of the groups. No significant changes in the weight, hematological parameters or clinical chemistry were noted between the control group and the experimental group. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues. Conclusion: The above findings suggest Scolopendrid Pharmacopuncture is a relatively safe to use for treatment. Further studies on the subject should be conducted to yield more concrete evidence.
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