Pietzner, Klaus;Nasser, Sara;Alavi, Sara;Darb-Esfahani, Silvia;Passler, Mona;Muallem, Mustafa Zelal;Sehouli, Jalid
Journal of Gynecologic Oncology
/
v.29
no.6
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pp.93.1-93.11
/
2018
The introduction of checkpoint inhibitors revolutionized immuno-oncology. The efficacy of traditional immunotherapeutics, like vaccines and immunostimulants was very limited due to persistent immune-escape strategies of cancer cells. Checkpoint inhibitors target these escape mechanisms and re-direct the immune system to anti-tumor toxicity. Phenomenal results have been reported in entities like melanoma, where no other therapy was able to demonstrate survival benefit, before the introduction of immunotherapeutics. The first experience in ovarian cancer (OC) was reported for nivolumab, a fully human anti-programmed cell death protein 1 (PD1) antibody, in 2015. While the data are extraordinary for a mono-immunotherapeutic agent and very promising, they do not match up to the revolutionary results in entities like melanoma. The key to exceptional treatment response in OC, could be the identification of the most immunogenic patients. We hypothyse that BRCA mutation could be a predictor of improved response in OC. The underlying DNA-repair-deficiancy should result in increased immunogenicity because of higher mutational load and more neoantigen presentation. This hypothesis was not tested to date and should be subject to future trials. The present article gives an overview of the immunologic background of checkpoint inhibition (CI). It presents current data on nivolumab and other checkpoint-inhibitors in solid tumors and OC specifically and depicts important topics in the management of this novel substance group, such as side effect control, diagnostic PD-1/programmed cell death-ligand 1 (PD-L1) expression assessment and management of pseudoprogression.
Background: The constant consumption of chemical products owing to expanding industrialization has led to an increase in public interest in chemical substances. As the production and disposal processes for these chemical products cause environmental problems, regional information on the hazard level of chemical substances is required considering their effects on humans and in order to ensure environmental safety. Objectives: This study aimed to identify hazard contribution and spatiotemporal characteristics by region and chemical by calculating a hazard-based result score using pollutant release and transfer register (PRTR) data. Methods: This study calculated the chemical discharge and hazard-based result score from the Risk-Screening Environmental Indicators (RSEI) model, analyzed their spatiotemporal patterns, and identified hotspot areas where chemical discharges and high hazard-based scores were concentrated. The amount of chemical discharge and hazard-based risk scores for 250 cities and counties across South Korea were calculated using PRTR data from 2011 to 2018. Results: The chemical discharge (high densities in Incheon, Daegu, and Busan) and hazard-based result scores (high densities in Incheon, Chungcheongnam-do, and some areas of Gyeongsangnam-do Province) showed varying spatial patterns. The chemical discharge (A, B) and hazard-based result score (C, D) hotspots were identified. Additionally, identification of the hazard-based result scores revealed differences in the type of chemicals contributing to the discharge. Ethylbenzene accounted for ≥80% of the discharged chemicals in the discharge hotspots, while chromium accounted for >90% of the discharged chemicals in the hazard-based result score hotspots. Conclusions: The RSEI hazard-based result score is a quantitative indicator that considers the degree of impact on human health as a toxicity-weighted value. It can be used for the management of industries discharging chemical substances as well as local environmental health management.
Mehmet Bulbul;Ali Tekce;Ebru Annac;Omer Korkmaz;Muhittin Onderci;Deniz Korkmaz;Akin Mustafa Demirci
Clinical and Experimental Reproductive Medicine
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v.50
no.1
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pp.34-43
/
2023
Objective: The aim of this study was to investigate the effect of royal jelly (RJ), a powerful natural antioxidant, on cyclophosphamide-induced ovarian damage. Methods: Thirty-two Wistar albino rats were divided into four groups. Oral treatment was administered to all rats for 16 days after a single intraperitoneal injection. The control group received intraperitoneal and oral saline; the RJ group received intraperitoneal saline and 100 mg/kg/day oral RJ; the cyclophosphamide group received intraperitoneal 100 mg/kg cyclophosphamide and oral saline; and the treatment group received intraperitoneal 100 mg/kg cyclophosphamide and 100 mg/kg/day oral RJ. The groups were compared in terms of ovarian reserve tests and histopathological changes in the ovary and uterus. Results: All follicle counts were higher in the treatment group than in the cyclophosphamide group. The increase in the number of preantral follicles (p=0.001) and the decrease in the number of atretic follicles (p=0.004) were statistically significant. RJ treatment significantly improved follicular degeneration and cortical fibrosis in the ovary and epithelial and gland degeneration in the uterus due to cyclophosphamide toxicity. Conclusion: According to these results, RJ reduces cyclophosphamide-related ovarian and endometrial damage in rats. For this reason, it should be further investigated to determine its effects on reproductive function.
Lee, Je Bong;Jeong, Mi-Hye;You, Are-Sun;Hong, Soonsung;Paik, Min-Kyoung;Oh, Jin-Ah;Park, Kyung Hun;Ihm, Yang Bin
The Korean Journal of Pesticide Science
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v.17
no.4
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pp.350-358
/
2013
Both 13-week and 1-year studies in dog were required for pesticide registration in domestic pesticide control authority. It is raising issue up whether to request 1-year dog study of pesticides using non-food crop. So at this investigation, relevant toxicity test to establish acceptable daily intake (ADI), target organs, difference of no-observed adverse-effect levels (NOAELs) in 13-week and 1-year of 166 active ingredients are analyzed. The data were evaluated to determine if the 13-week dog study and the long term studies in two rodent species (mice and rats) without 1-year dog study were sufficient for the identification of NOAELs and lowest observed adverse effect levels (LOAELs) for the derivation of ADI. Toxicity end points and dose response data from 13 week and 1-year studies were compared. The analysis showed that 68 ADIs of the 166 pesticides were established from dog studies. Major target organs of dog studies were liver in 49 cases, body weight change in 21 cases, cholinesterase inhibition in 16 cases, and alteration in hematology in 14 cases. Similarity of target organ in 13-week and 1-year was 73%. 22 of 40 pesticides had similar critical effects regardless of duration and had NOAELs within a difference of 1.5-fold of each other. For the remaining 18 pesticides, 14 items had lower NOAELs in the 1-year study than 13-week study primarily due to dose selection and spacing. In only 10% of the cases were additional toxic effects identified in the 1-year study that were not observed in the 13-week study.
Park, Na-Hye;Lee, Hwa-Yong;Choi, Jong-Woon;Park, Seung-Chun
The Korean Journal of Mycology
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v.46
no.3
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pp.295-306
/
2018
In the present study, we compared the effects of 50% ethanolic extracts of Chinese and Korean Wolfiporia cocos (CPE and KPE) on in vitro lipid accumulation in 3T3-L1 cells and their anticancer activities in Sarcoma 180 cells. We further compared the anticancer activities and the 50% inhibitory concentrations ($IC_{50}$) of CPE with KPE with cultivated for one and two years in a landfill and a facility (LPE and FPE), respectively. In addition, the single oral dose toxicities of CPE and KPE were evaluated in mice. Lipid accumulation was inhibited after 48 hours, in CPE and KPE treated 3T3-L1 cells; however, no significant difference was observed between CPE and KPE in their lipid accumulation inhibitory activities. The anticancer activity of KPE was higher than that of CPE at $300{\mu}g/mL$ (p<0.05), revealing the possibility of an auxiliary biological means for origin identification. The anticancer activities of LPE and FPE were significantly stronger than that of CPE (p<0.05) but there was no difference between extracts from one- and two-year-old W. cocos, irrespective of the cultivation method. In single oral dose toxicity tests, CPE and KPE did not induce mortality during the 14-day observation. Thus, the 50% of lethal dose ($LD_{50}$) of CPE and KPE were estimated to be higher than 2,000 mg/kg. Taken together, our results indicate that the anticancer assay could be an auxiliary means of identifying the origin of W. cocos. In addition, artificial cultivation could be an alternative way to reduce the import of W. cocos. Lastly, 50% ethanolic W. cocos extracts could be potential candidates for obesity and cancer managements.
Entomopathogenic fungus Cordyceps militaris is famous for its medicinal efficacies. It has been reported to have various pharmacological activities such as anti-tumour, insecticidal, antibacterial, immunomodulatory and antioxidant. In this study, we investigated the effect of the extract of C. militaris (MPUN8501), which was identified by the analysis of the nucleotide sequences of 5.8S ribosomal RNA, on the function of liver. C. militaris powder was extracted using hot water extracts method as time, volume and temperature and using method as differential polarity of organic solvent. Each fraction was tested for the improvement of hepatic enzyme alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activity. The BuOH extracts (CME) had highest activity which was used for the test of toxicity and efficacy of C. militaris. The enhancing effect of CME on the activity of ADH and ALDH was much more than medicine, drink, natural tea etc. Thus CME promoted the resolution of alcohol and acetaldehyde in rats, inducing recovery to normal condition rapidly. Furthermore, oral administration of CME effectively protected the carbon tetrachloride-induced acute hepatic injury as revealed by the hematological parameters (levels of sGOT and sGPT) and histological observation. CME was ascertained to be safe by regulatory toxicity studies of single dose toxicity and genotoxicity. These results suggest that CME would be useful for the maintaining normal hepatic activity as a functional health food.
Recently, plastic waste in Korea has been recognized as a critical issue due to an increase in massive production of plastics, difficulty in disposal of waste plastics, and public recognition of toxicity in micro-plastics, etc. To resolve those problems, the regulation to reduce plastics consumption may be primarily considered but, in this case, clarification should be made on the rationales and the action plans in the regulation for individual waste plastic items. Another problem is the small capital sizes of domestic recycling companies, which leads to poor R&D capacity, low recycling yields and thus lowering values of recycling items. This adversely affects consumers' perception. The R&D toward recycling technical progress should take into account the environmental friendliness and recyclability from the early product design stages. Certainly, this should be supported in governmental policy and public action plans. In addition, by referring to advanced policies of i.e. European Union, the recycling industry should be recognized as an opportunity toward new investment & employment. If necessary, the regulation of plastic consumption through a formal evaluation process such as Life Cycle Assessment (LCA) will also be helpful. The values of recycled plastics should be improved through the identification and elimination of harmful chemical substances potentially contained in the products.
Qi, Xu Feng;Li, Ming Shun;Choi, Jae-Young;Roh, Jong-Yul;Song, Ji Zhen;Wang, Yong;Jin, Byung-Rae;Je, Yeon-Ho;Li, Jian Hong
International Journal of Industrial Entomology and Biomaterials
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v.18
no.1
/
pp.18-27
/
2009
B. thuringiensis strain LY-99 belonging to subsp. alesti (H3a3c), was isolated from Chinese tobacco warehouse and showed significantly high toxicity to Plutella xylostella. For the identification of the cry1-type genes from B. thuringiensis LY-99, an extended multiplex PCRrestriction fragment length polymorphism (PCRRFLP) method was established by using two pairs of universal primers based on the conserved regions of the cry1-type genes to amplify around 2.4 kb cry1-type gene fragments. Then the DNA fragment was cloned into pGEM-T Easy vector and digested with EcoRI and EcoRV enzymes. Through this method, a known cry1-type gene was successfully identified from the reference strain, B. thuringiensis subsp. alesti. In addition, the RFLP patterns revealed that B. thuringiensis LY-99 included a novel cry1A-type gene in addition to cry1Aa, cry1Ac, cry1Be and cry1Ea genes. The novel cry1A-type gene was designated cry1Ah2 (Genbank accession No DQ269474). An inverse PCR method was used to amplify the flank regions of cry1Ah2 gene. Finally, 3143 bp HindIII fragment from B. thuringiensis LY-99 plasmid DNA including 5' region and partial ORF was amplified, and sequence analysis revealed that cry1Ah2 gene from LY-99 showed 89.31% of maximum sequence similarity with cry1Ac1 crystal protein gene. In addition, the deduced amino acid sequence of Cry1Ah2 protein shared 87.80% of maximum identity with that of Cry1Ac2. This protein therefore belongs to a new class of B. thuringiensis crystal proteins.
Purpose: The purpose of this study was to investigate the needs of home care nursing services in relation to the patients in hospital. Method: Subjects were 129 patients who admitted hospital and were selected through convenience sampling. Data were collected using the Home Health Care Need Assessment Questionnaire constructed by the Korea Health Industry Development Institute. Data were analyzed using SAS 8.12 program by applying percentage. Results: 1. According to the diagnosis of the subjects, the majority had cancer (25.0%), followed by musculoskeletal disease (15,6%), neuro/cerebral vascular disease (14.1%), digestive (10.9%) and respiratory disease (10.9%). 2. With regard to fundamental nursing service, subjects wanted to receive home care services for the following reasons: Problem identification and diagnosis (77.5%), vital sign check (49.6%); and intake and output measure (20.9%). 3. With regard to clinical laboratory tests, 62.8% wanted to receive blood tests, and followed by urine tests 26.4%, and wound drainage 26.4%. 4. With regard to medication and treatment service, 40.3% of the subjects wanted to receive intravenous fluid therapy, 26.4% intravenous antibiotics, and 26.4% the monitoring of fluid therapy. 5. With regard to therapeutic nursing service, 33.3% wanted to receive wound care, 26.4% ROM exercise, and 27.9% foley catheter change and care. 6. With regard to educational needs, 42.6% wanted education on infection monitoring, 41.4% on medication, and 34.9% on diet. 7. With regard to counseling needs, 65.9% wanted to receive telephone counseling about patient condition, 52.7% counseling about re-admission and 51.9% direct counseling about patient condition. In the group of injury and toxicity, and cardiovascular/circulatory diseases, 100% wanted telephone and direct counseling about the patient condition. Conclusion: Therefore, in order to improve the quality of hospital based home health care services, various factors that affect to the need of home health care should be analyzed and specified nursing care should be looked into.
Background: Many clinical trials have been conducted to evaluate sorafenib for the treatment of advanced NSCLC, but the results for efficacy have been inconsistent. The aim of this study was to evaluate the efficacy and safety of sorafenib in patients with advanced NSCLC in more detail by meta-analysis. Methods: This meta-analysis of randomized controlled trials (RCTs) was performed after searching PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, and the proceedings of major conferences for relevant clinical trials. Two reviewers independently assessed the quality of the trials. Outcomes analysis were disease control rate (DCR), progression- free survival (PFS), overall survival (OS) with 95% confidence intervals (CI) and major toxicity. Subgroup analysis was conducted according to sorafenib monotherapy, in combination with chemotherapy or EGFR-TKI to investigate the preferred therapy strategy. Results: Results reported from 6 RCTs involving 2, 748 patients were included in the analysis. Compared to sorafenib-free group, SBT was not associated with higher DCR (RR 1.31 (0.96- 1.79), p=0.09), PFS (HR 0.82 (0.66-1.02), p=0.07) and OS (HR 1.01 (0.92-1.12), p=0.77). In terms of subgroup results, sorafenib monotherapy was associated with significant superior DCR and longer PFS, but failed to show advantage with regard to OS. Grade 3 or greater sorafenib-related adverse events included fatigue, hypertension, diarrhea, oral mucositis, rash and HFSR. Conclusions: SBT was revealed to yield no improvement in DCR, PFS and OS. However, sorafenib as monotherapy showed some activity in NSCLC. Further evaluation may be considered in subsets of patients who may benefit from this treatment. Sorafenib combined inhibition therapy should be limited unless the choice of platinum-doublet regimen, administration sequence or identification of predictive biomarkers are considered to receive better anti-tumor activity and prevention of resistance mechanisms.
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