Background: Previous research has suggested that single doses of a standardised Panax ginseng extract can decrease fasted blood-glucose levels and modulate cognitive performance in healthy young volunteers. The latter has generally been seen in terms of improved secondary memory performance. However, both the cognitive effects of chronic administration of ginseng and the potential modulation of working memory have received comparatively little research attention. Aims: The current double-blind, placebo-controlled, balanced cross-over study investigated the effects of 8-weeks administration of Korean ginseng extract (200 mg) on cognitive performance, gluco-regulatory parameters and ratings of subjective mood and 'quality of life'. Methods: 'Eighteen healthy young participants were assessed pre-dose and 3 hours post-dose on the mornings of Day 1, Day 29 and Day 57 of 8 week treatment regimens of both placebo and ginseng. A four-week placebo wash-out separated the treatment phases. Each assessment included the Cognitive Drug Research battery, computerised working memory tasks, and Bond-Lader mood scales. The WHO Quality of Life scale (WHOQOL-BREF) was completed once per visit. Gluco-regulatory parameters were assessed with assays of blood glucose, insulin and HbA1c. Results: Data from the 16 participants that completed the study showed that there were no significant, acute treatment related differences on Day 1 of treatment, or in gluco-regulatory parameters throughout the study. However, time related performance improvements were evident following chronic administration of ginseng on the '3-Back' and 'Corsi-block' computerised working memory tasks. Ginseng was also associated with an improved score on the 'social relations' subscale of the WHOQOL-100, and a significant shift on the 'calm' factor of the Bond-Lader mood scales (from calm/relaxed towards excited/tense). Conclusion: The results of the current study suggest that Korean ginseng extract can modulate working memory performance and subjective ratings of 'quality of life' and mood. Replication with a larger sample size may further elucidate the actions of this product.
Exposure to formaldehyde(FA) is closely associated with adverse health effects such as irritation, inflammation, and squamous cell carcinomas of the nasal cavities. Owing to its rapid metabolism and elimination, exposure to FA does not always result in an increased concentration in blood or urine of animals and humans. Therefore, the development of biomarkers for FA exposure is necessary for risk assessment. In the present study, the effects of FA were investigated on the expression of genes involved in the MAPK pathway in vitro and results confirmed in rats exposed to FA by inhalation. Treatment of Hs 680.Tr human tracheal epithelial cells with FA induced gene expression for PDGFA, TNFSF11, SHC1, and HRAS. HRAS expression was also increased in tracheas of rats exposed to FA. In addition, FA exposure induced the expression of RASSF4, a member of the Rasassociation domain family of Ras effectors, in rat tracheas. In conclusion, data showed FA-inducible expression of genes involved in the MAPK pathway occurred and increased expression of HRAS and RASSF4 was noted in rat tracheas subchronically exposed to FA by inhalation. These genes may serve as molecular targets of FA toxicity facilitating the understanding of the toxic mechanism.
Polypharmacy is increasing owing to an increase in the elderly population and multimorbidities associated with the increased risk of administration of potentially inappropriate medications (PIMs). The negative effects of polypharmacy on various health conditions and aspects, such as fall, fracture, mortality, cognitive function, and dementia, have been reported. The management of excess and inappropriate polypharmacy through proper interventions and local or national guidelines has been highlighted. The purpose of polypharmacy management is to appropriately prescribe medicines that are essential to treat diseases in patients and to avoid inappropriate polypharmacy, such as interactive or duplicate medicines under prescription and PIMs for specific diseases. Community pharmacists in Australia, the EU, USA, and Japan are collaborating with prescribers to review medications to ensure that the patients can be prescribed appropriate medications. The service cost is reimbursed by public or private insurers. A study in the United States has shown that even with medication review costs, the overall medication cost has reduced. In Korea, various projects such as Drug Utilization Review service and safe use of medicines have been conducted; however, no national guidelines or management measures have been established. It is necessary to implement a national long-term plan on polypharmacy management. Furthermore, a phased implementation plan is required. Shortly, active medication review services and education programs for healthcare professionals with the support of the government should be considered in Korea with reference to other countries in order to raise awareness of seriousness and risks of inappropriate polypharmacy.
Objective: Over the last several years, immunotherapy has become one of the most promising therapeutic options for cancer. This study aims to summarize the updates on cancer immunotherapy focusing on immune checkpoint inhibitors, such as programmed cell death-1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, which have received attention as new anticancer therapeutic agents. Methods: A literature survey was carried out on PubMed to identify high-impact papers on cancer immunotherapy from 2010. The most recent data on clinical efficacy and safety have been included highlighting the response characteristics to recently approved immunotherapeutic agents. Results: In various cancers, immune checkpoints are a means for cancer cells to evade the immune system. Furthermore, CTLA-4 and PD-L1 can be overexpressed, allowing malignant cells to evade T-cells. Numerous clinical trials have been performed to seek appropriate indication of these products in various cancer types. Among them, the most conspicuous types are melanoma, non-small-cell lung cancer, and head and neck cancer. The approval of ipilimumab by Food and Drug Administration (FDA) commenced a new era of cancer immunotherapy. This was followed by the approval of nivolumab and pembrolizumab. Currently, combination therapies are being investigated for various cancer types. Conclusion: In this study, we reviewed recently reported scientific and clinical evidence for currently approved immune checkpoint inhibitors. Although these novel checkpoint inhibitors are ever evolving for cancer therapies, there exist limitations that need to be overcome, indicating the necessity for further studies aiming to improve their efficacy, toxicity, and cost.
Objectives: Improving public capability to obtain, understand, and use health information is important for decision-making and communication. This study attempts to measure adults' literacy of the information provided by a public health institution. Factors affecting different health literacy level are also investigated. The relation between public risk perception and health literacy is examined as well. Methods: A total of 800 korean adults were surveyed. To provide the participants health literacy questions, health messages of heavy metals released by KFDA as well as literacy questions developed by NIKL were used. A total of eight questions were developed to measure health literacy. The dimensions of risk perception proposed by Brewer et al.(2008) were modified to measure risk perception. Results: The average percentage of correct answer for all literacy questions was only 65.57%. Individuals at the older age, and with lower education/ income level were more likely to be low literate. In addition, health literacy was strongly associated with risk perception. Conclusions: Public literacy of health information is influenced by socio demographic factors. This study suggested a possibility that low health literacy may affect unrealistically high risk perception. Further studies with sophisticated methodologies to measure health literacy need to be developed.
Colorectal cancer is a very prevalent diagnosed cancer. The current study was performed in order to examine the role of BRAE (Basella rubra aqueous extract) in regulating aberrant crypt foci (ACF) formation, cell proliferation and inhibition of apoptosis in a colon carcinogenesis model in male Wistar rats. Rats were randomly allocated into six groups. Group I served as control, and group II acted as a drug control administered BRAE (250mg/kg b.w.) orally for 30 weeks. Rats in group III-VI were given subcutaneous injections of DMH (25mg/kg b.w. weekly) for 15 weeks to initiate colon carcinogenesis. Those in group IV and VI were administered BRAE along with DMH injections. Rats in group V were administered with BRAE after cessation of DMH injection. After 30 weeks of experimental period colons were obtained from experimental groups and analyzed for ACF incidence, argyrophilic nucleolar organizing region-associated proteins (AgNOR) count, histopathological and immunohistochemical changes. Only in DMH exposed groups were ACF and AgNOR numbers increased. Administration of BRAE appreciably decreased the numbers of ACF and AgNOR in BRAE treated groups. Histopathological findings revealed a high level of dysplastic changes with decreased number of goblet cells found only in only DMH injected rats. Administration of BRAE in treated group rats reversed these changes. Expression markers for cell proliferation (PCNA and Ki67) were elevated in DMH treated rats, but reduced with BRAE treatement. This expression was reversed with apoptosis markers (p53 and Caspase-3). Thus the results results of the present study were found to be significant and confirmed the potential efficacy of BRAE against colon carcinogenesis.
Background and Objective: Histone deacetylase (HDAC) inhibitors represent a promising class of potential anticancer agents for treatment of human malignancies. In this study, we investigated the effect of trichostatin A (TSA), one such HDAC inhibitor, in combination with docetaxel (TXT), a cytotoxic chemotherapy agent or erlotinib, a novel molecular target therapy drug, on lung cancer A549 cells. Methods: A549 cells were treated with TXT, erlotinib alone or in combination with TSA, respectively. Cell viability, apoptosis, and cell cycle distribution were evaluated using MTT (3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide) assay, Hochst33258 staining and flow cytometry. Moreover, immunofluorescent staining and Western blot analysis were employed to examine alterations of ${\alpha}$-tubulin, heat shock protein 90 (hsp90), epidermal growth factor receptor (EGFR), and caspase-3 in response to the different exogenous stimuli. Results: Compared with single-agent treatment, co-treatment of A549 cells with TSA/TXT or TSA/erlotinib synergistically inhibited cell proliferation, induced apoptosis, and caused cell cycle delay at the $G_2/M$ transition. Treatment with TSA/TXT or TSA/erlotinib led to a significant increase of cleaved caspase-3 expression, also resulting in elevated acetylation of ${\alpha}$-tubulin or hsp90 and decreased expression of EGFR, which was negatively associated with the level of acetylated hsp90. Conclusions: Synergistic anti-tumor effects are observed between TXT or erlotinib and TSA on lung cancer cells. Such combinations may provide a more effective strategy for treating human lung cancer.
TEL-AML1 fusion oncogene (t 12; 21) is the most common chromosomal abnormality in childhood acute lymphoblastic leukemia (ALL). This translocation is associated with a good prognosis and rarely shows chemotherapeutic resistance to 3-drug based remission induction phase of treatment as well as overall treatment. Thus, the higher the frequency of this fusion oncogene, the easier to manage childhood ALL in a given region with less intensive chemotherapy. Although global frequency of TEL-AML1 has been reported to be 20-30%, a very low frequency has been found in some geographical regions, including one study from Lahore, Punjab, Pakistan and others from India. The objective of present study was to investigate if this low frequency of TEL-AML1 in pediatric ALL is only in Lahore region or similar situation exists at other representative oncology centers of Pakistan. A total of 167 pediatric ALL patients were recruited from major pediatric oncology centers situated in Lahore, Faisalabad, Peshawar and Islamabad. Patients were tested for TEL-AML1 using nested reverse transcription polymerase chain reaction (RT-PCR). Only 17 out of 167 (10.2%) patients were found to be TEL-AML1 positive. TEL-AML1+ALL patients had favorable prognosis, most of them (82.4%, 14/17) showing early remission and good overall survival. Thus, our findings indicate an overall low frequency of TEL-AML1 in Pakistan pediatric ALL patients, in accordance with lower representation of this prognostically important genetic abnormality in other less developed countries, specifically in south Asia, thus associating it with poor living standards in these ethnic groups. It also indicates ethnic and geographical differences in the distribution of this prognostically important genetic abnormality among childhood ALL patients, which may have a significant bearing on ALL management strategies in different parts of the world.
Aim: To determine whether induced abortion (IA) increases breast cancer (BC) risk. Materials and Methods: A population-based case-control study was performed from Dec, 2000 to November, 2004 in Shanghai, China, where IA could be verified through the family planning network and client medical records. Structured questionnaires were completed by 1,517 cases with primary invasive epithelial breast cancer and 1,573 controls frequency-matched to cases for age group. The information was supplemented and verified by the family planning records. Statistical analysis was conducted with SAS 9.0. Results: After adjusting for potential confounders, induced abortions were not found to be associated with breast cancer with OR=0.94 (95%CI= 0.79-1.11). Compared to parous women without induced abortion, parous women with 3 or more times induced abortion (OR=0.66, 95%CI=0.46 to 0.95) and women with 3 or more times induced abortion after the first live birth (OR=0.66, 95%CI =0.45 to 0.97) showed a lower risk of breast cancer, after adjustment for age, level of education, annual income per capita, age at menarche, menopause, parity times, spontaneous abortion, age at first live birth, breast-feeding, oral contraceptives, hormones drug, breast disease, BMI, drinking alcohol, drinking tea, taking vitamin/calcium tablet, physical activity, vocation, history of breast cancer, eating the bean. Conclusions: The results suggest that a history of induced abortions may not increase the risk of breast cancer.
Masbi, Mohammad Hosein;Mohammadiasl, Javad;Galehdari, Hamid;Ahmadzadeh, Ahmad;Tabatabaiefar, Mohammad Amin;Golchin, Neda;Haghpanah, Vahid;Rahim, Fakher
Asian Pacific Journal of Cancer Prevention
/
v.15
no.5
/
pp.2027-2033
/
2014
Background: We aimed to assess RET proto-oncogene polymorphisms in three different Iranian families with medullary thyroid cancer (MTC), and performed molecular dynamics simulations and free energy stability analysis of these mutations. Materials and Methods: This study consisted of 48 patients and their first-degree relatives with MTC confirmed by pathologic diagnosis and surgery. We performed molecular dynamics simulations and free energy stability analysis of mutations, and docking evaluation of known RET proto-oncogene inhibitors, including ZD-6474 and ponatinib, with wild-type and mutant forms. Results: The first family consisted of 27 people from four generations, in which nine had the C.G2901A (P.C634Y) mutation; the second family consisted of six people, of whom three had the C.G2901T (P.C634F) mutation, and the third family, who included 12 individuals from three generations, three having the C.G2251A (P.G691S) mutation. The automated 3D structure of RET protein was predicted using I-TASSER, and validated by various protein model verification programs that showed more than 96.3% of the residues in favored and allowed regions. The predicted instability indices of the mutated structures were greater than 40, which reveals that mutated RET protein is less thermo-stable compared to the wild-type form (35.4). Conclusions: Simultaneous study of the cancer mutations using both in silico and medical genetic procedures, as well as onco-protein inhibitor binding considering mutation-induced drug resistance, may help in better overcoming chemotherapy resistance and designing innovative drugs.
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