Background: PI3/AKT and NF-kB signaling pathways are constitutively active in acute myeloid leukemia and cross-talk between the two has been shown in various cancers. However, their role in acute myeloid leukemia has not been completely explored. We therefore used cell penetrating inhibitor peptides to define the contributions of AKT and NF-kB to survival and multi drug resistance (MDR) in HL-60 cells. Materials and Methods: Inhibition of AKT and NF-kB activity by AKT inhibitor peptide and NBD inhibitor peptide, respectively, resulted in decreased expression of mRNA for the MDR1 gene as assessed by real time PCR. In addition, treatment of HL-60 cells with AKT and NBD inhibitor peptides led to inhibition of cell viability and induction of apoptosis in a dose dependent manner as detected by flow cytometer. Results: Finally, co-treatment of HL-60 cells with sub-optimal doses of AKT and NBD inhibitor peptides led to synergistic apoptotic responses in AML cells. Conclusions: These data support a strong biological link between NF-kB and PI3-kinase/AKT pathways in the modulation of antiapoptotic and multi drug resistant effects in AML cells. Synergistic targeting of these pathways using NF-kB and PI3-kinase/AK inhibitor peptides may have a therapeutic potential for AML and possibly other malignancies with constitutive activation of these pathways.
Background: Up-regulation of hsp90 gene expression occurs in numerous cancers such as lung cancer. D,L-lactic-co-glycolic acid-poly ethylene glycol-17-dimethylaminoethylamino-17-demethoxy geldanamycin (PLGA-PEG-17DMAG) complexes and free 17-DMAG may inhibit the expression. The purpose of this study was to examine whether nanocapsulating 17DMAG improves the anti cancer effect over free 17DMAG in the A549 lung cancer cell line. Materials and Methods: Cells were grown in RPMI 1640 supplemented with 10% FBS. Capsulation of 17DMAG is conducted through double emulsion, then the amount of loaded drug was calculated. Other properties of this copolymer were characterized by Fourier transform infrared spectroscopy and H nuclear magnetic resonance spectroscopy. Assessment of drug cytotoxicity on the grown of lung cancer cell line was carried out through MTT assay. After treatment, RNA was extracted and cDNA was synthesized. In order to assess the amount of hsp90 gene expression, real-time PCR was performed. Results: In regard to the amount of the drug load, IC50 was significant decreased in nanocapsulated(NC) 17DMAG in comparison with free 17DMAG. This was confirmed through decrease of HSP90 gene expression by real-time PCR. Conclusions: The results demonstrated that PLGA-PEG-17DMAG complexes can be more effective than free 17DMAG in down-regulating of hsp90 expression by enhancing uptake by cells. Therefore, PLGA-PEG could be a superior carrier for this kind of hydrophobic agent.
Tahory, Hale;Mohammadian, Robab;Rahmani, Azad;Seyedrasooli, Alehe;Lackdezajy, Sima;Heidarzadeh, Mehdi
Asian Pacific Journal of Cancer Prevention
/
제17권2호
/
pp.755-758
/
2016
Background: There is little information about the objectivity of posttraumatic growth experienced by cancer patients. So, the aim of present study was to investigate the viewpoints of family caregivers regarding posttraumatic growth in cancer patients. Materials and Methods: This descriptive study was conducted in one referral medical center in East Azerbaijan Province in northwest of Iran. 120 primary family caregivers of cancer patients participated with a convenience sampling method. The Posttraumatic Growth Inventory (PTGI) and Perception about Prognosis Scale (PPS) were applied for data collection with analysis performed using SPSS statistical software. Results: Family caregivers believed that their patients had a good prognosis (score 3.95 from 5). The total score of PTGI was 60.7 (SD=18.8) that indicates a moderate level of growth as reported by family caregivers. Conclusions: Family caregivers of cancer patients have incorrect viewpoints about the prognosis of their patients and reported moderate levels of growth. These findings showed that posttraumatic growth among cancer patients is an objective phenomenon.
Richards, John R.;Stayton, Taylor L.;Wells, Jason A.;Parikh, Aman K.;Laurin, Erik G.
Clinical and Experimental Emergency Medicine
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제5권4호
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pp.240-248
/
2018
Objective Determine differences between faculty, residents, and nurses regarding night shift preparation, performance, recovery, and perception of emotional and physical health effects. Methods Survey study performed at an urban university medical center emergency department with an accredited residency program in emergency medicine. Results Forty-seven faculty, 37 residents, and 90 nurses completed the survey. There was no difference in use of physical sleep aids between groups, except nurses utilized blackout curtains more (69%) than residents (60%) and faculty (45%). Bedroom temperature preference was similar. The routine use of pharmacologic sleep aids differed: nurses and residents (both 38%) compared to faculty (13%). Residents routinely used melatonin more (79%) than did faculty (33%) and nurses (38%). Faculty preferred not to eat (45%), whereas residents (24%) preferred a full meal. The majority (>72%) in all groups drank coffee before their night shift and reported feeling tired despite their routine, with 4:00 a.m. as median nadir. Faculty reported a higher rate (41%) of falling asleep while driving compared to residents (14%) and nurses (32%), but the accident rate (3% to 6%) did not differ significantly. All had similar opinions regarding night shift-associated health effects. However, faculty reported lower level of satisfaction working night shifts, whereas nurses agreed less than the other groups regarding increased risk of drug and alcohol dependence. Conclusion Faculty, residents, and nurses shared many characteristics. Faculty tended to not use pharmacologic sleep aids, not eat before their shift, fall asleep at a higher rate while driving home, and enjoy night shift work less.
Background: Previous studies have observed an association between ABO blood group and risk for certain gastrointestinal malignancies, including pancreatic and gastric cancer. However, it is unclear whether there is such an association with colorectal cancer (CRC). In this study, possible relationships between ABO blood groups and Rh factor and KRAS status in patients with CRC were investigated. Materials and Methods: In 1,620 patients with CRC, blood group and Rh factor were examined and compared with the control group of 3,022,883 healthy volunteer blood donors of the Turkish Red Crescent between 2004 and 2011. The relationship of blood groups with wild type K-ras status was also evaluated. Results: Overall distributions of ABO blood groups as well as Rh factor were comparable between patients (45% A, 7.2% AB, 16.4% B, 31.4% O, and 87.2% Rh+) and controls (42.2% A, 7.6% AB, 16.3% B, 33.9% O, and 87.7% Rh+) (p=0.099). However, there were statistically significant difference between patients and controls with respect to O vs. non O blood group (p=0.033) and marginally significant difference for A vs. non-A blood group (p=0.052). Among patients, the median age was 62 (range 17-97), 58.1% were male. There were no statistically significant differences respect to sex and K-ras status. Conclusion: In present study, the ABO/Rh blood groups were statistically significantly associated with the risk of CRC. There were no relationship between K-ras status and ABO blood group and Rh factor. However further studies with larger numbers of patients are needed to establish the role of blood groups and to define t he mechanisms by which ABO blood type affect CRC.
Gunduz, Seyda;Mutlu, Hasan;Goksu, Sema Sezgin;Arslan, Deniz;Tatli, Ali Murat;Uysal, Mukremin;Coskun, Hasan Senol;Bozcuk, Hakan;Ozdogan, Mustafa;Savas, Burhan
Asian Pacific Journal of Cancer Prevention
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제15권20호
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pp.8843-8846
/
2014
Background: Malignant mesothelioma (MM) is almost always fatal and few treatment options are available. The aim of this study was to evaluate the efficacy of oral cyclophosphamide and etoposide for patients who underwent standard treatment for advanced MM. Materials and Methods: This study included 22 malignant pleural mesothelioma patients who were treated with oral cyclophosphamide and etoposide (EE). Results: The average follow-up period of the patients was 39.1 months. Under the treatment of oral EE, median progression-free survival was 7.7 months [95%CI HR (4.3-11.1)] and median overall survival was 28.1 months [95%CI HR (5.8-50.3)]. The treatment response rates were as follows: 4 patients (27.3%) had a partial response (PR), 12 (54.5%) had stable disease (SD), and progressive disease (PD) was observed in 6 (35.9%). Conclusions: Oral EE can be administered effectively to patients with inoperable malignant mesothelioma who had previously received standard treatments.
Background: With limited information available, the association among urinary tract infections, urease-producing bacteria and the presence of magnesium ammonium phosphate (MAP) urolithiasis in canines in Thailand requires more study. Objectives: This study aimed to investigate the association between demographic characteristics of canines and the presence of MAP urolithiasis in canines, and to evaluate antimicrobial susceptibility patterns of bacteria isolated from canine uroliths. Methods: A total of 56 canines admitted for treatment with surgical removal of uroliths were recruited. Demographic characteristics and clinical chemistry data were recorded. Bacteria isolated from the removed uroliths were identified. Chemical compositions of the uroliths were analyzed by Fourier transform infrared spectrometer. Potential risk factors were determined with univariable and multivariable logistic regression analyses. Results: Of 56 canine urolithiasis, bacteria were isolated from uroliths of 38 canines (27 MAP and 11 non-MAP) but not from uroliths of 18 canines (5 MAP and 13 non-MAP). The most common bacteria found in nidus of MAP uroliths was Staphylococcus pseudintermedius (approximately 51%). An antimicrobial resistance was frequently found in Staphylococci isolates (42.86%). Multivariate logistic regression analysis showed that the predictors of MAP urolith in canine urolithiasis were being female (p = 0.044; adjusted odds ratio [OR], 10.22; 95% confidence interval [CI], 1.06-98.24) and the positive urolith culture (p = 0.012; adjusted OR, 8.60; 95% CI, 1.60-46.30). Conclusions: Our results indicate that S. pseudintermedius (a urease-producing bacterium) is the major causative bacteria of MAP uroliths. A positive urolith culture and being female are risk factors of MAP urolithiasis in canines.
Gold nanoparticles (GNPs) were conjugated with gallic acid (GA) at various concentrations between 30 and $150{\mu}M$ and characterized using transmission electron microscopy (TEM) and UV-Vis spectroscopy (UV-VIS). The anticancer activities of the gallic acid-stabilized gold nanoparticles against well-differentiated (M213) and moderately differentiated (M214) adenocarcinomas were then determined using a neutral red assay. The GA mechanism of action was evaluated using Fourier transform infrared (FTIR) microspectroscopy. Distinctive features of the FTIR spectra between the control and GA-treated cells were confirmed by principal component analysis (PCA). The surface plasmon resonance spectra of the GNPs had a maximum absorption at 520 nm, whereas GNPs-GA shifted the maximum absorption values. In an in vitro study, the complexed GNPs-GA had an increased ability to inhibit the proliferation of cancer cells that was statistically significant (P<0.0001) in both M213 and M214 cells compared to GA alone, indicating that the anticancer activity of GA can be improved by conjugation with GNPs. Moreover, PCA revealed that exposure of the tested cells to GA resulted in significant changes in their cell membrane lipids and fatty acids, which may enhance the efficacy of this anticancer activity regarding apoptosis pathways.
Background: The aims of this study were compare the serum visfatin and resistin levels between endometrial cancer (EC) patients and controls and evaluate their power to predict prognosis. Materials and Methods: This prospective study was conducted between March 2013 to June 2014 on the Gynecologic Oncology Department of the University of Selcuk, Konya, Turkey. A total of 42 EC patients and 42 controls were included and assessed for differences in serum visfatin and resistin levels, along with prognostic factors. Results: Endometrial cancer patients had significantly higher visfatin levels than control s (p: 0.011), associated with deep myometrial invasion (p: 0.019). In contrast the serum level of resistin did not significantly differ between EC patients and controls (p: 0.362). However, high resistin level in EC patients was associated with increase lymph node metastasis (p: 0.009). On logistic regression analysis, we found that serum visfatin elevation was associated with risk of myometrial invasion (OR: 1,091; 95%CI: 1.021-1.166; p: 0.010) and serum resistin with risk of lymph node metastasis (OR: 1.018; 95%CI: 1.000-1.035; p: 0.046). For myometrial invasion prediction, a serum visfatin level greater than 26.8 ng/mL demonstrated a sensitivity and specificity of 66.6 % and 96.4%, respectively. For lymph node metastasis prediction, the best cut-off for serum resistin level was 599ng/mL. A serum resistin level greater than this demonstrated a sensitivity and specificity of 87.5% and 77.1%, respectively. Conclusions: Our data suggest that serum visfatin is elevated in patients with EC and serum visfatin and resistin levels could be used to predict the risk of advance stage lesions.
Background: Non-epithelial malignant ovarian tumors and clear cell carcinomas, Brenner tumors, transitional cell tumors, and carcinoid tumors of the ovary are rare ovarian tumors (ROTs). In this study, our aim was to determine the clinicopathological features of ROT patients and prognostic factors associated with survival. Materials and Methods: A total of 167 patients with ROT who underwent initial surgery were retrospectively analyzed. Prognostic factors that may influence the survival of patients were evaluated by univariate and multivariate analyses. Results: Of 167 patients, 75 (44.9%) were diagnosed with germ-cell tumors (GCT) and 68 (40.7%) with sex cord-stromal tumors (SCST); the remaining 24 had other rare ovarian histologies. Significant differences were found between ROT groups with respect to age at diagnosis, tumor localization, initial surgery type, tumor size, tumor grade, and FIGO stage. Three-year progression-free survival (PFS) rates and median PFS intervals for patients with other ROT were worse than those of patients with GCT and SCST (41.8% vs 79.6% vs 77.1% and 30.2 vs 72 vs 150 months, respectively; p=0.01). Moreover, the 3-year overall survival (OS) rates and median OS times for patients with both GCT and SCST were better as compared to patients with other ROT, but these differences were not statistically significant (87.7% vs 88.8% vs 73.9% and 170 vs 122 vs 91 months, respectively; p=0.20). In the univariate analysis, tumor localization (p<0.001), FIGO stage (p<0.001), and tumor grade (p=0.04) were significant prognostic factors for PFS. For OS, the univariate analysis indicated that tumor localization (p=0.01), FIGO stage (p=0.001), and recurrence (p<0.001) were important prognostic indicators. Multivariate analysis showed that FIGO stage for PFS (p=0.001, HR: 0.11) and the presence of recurrence (p=0.02, HR: 0.54) for OS were independent prognostic factors. Conclusions: ROTs should be evaluated separately from epithelial ovarian cancers because of their different biological features and natural history. Due to the rarity of these tumors, determination of relevant prognostic factors as a group may help as a guide for more appropriate adjuvant or recurrent therapies for ROTs.
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