RESUMEN
The treatment of advanced prostate cancer remains a formidable challenge due to the limited availability of effective treatment options. Therefore, it is imperative to identify promising druggable targets that provide substantial clinical benefits and to develop effective treatment strategies to overcome therapeutic resistance. Cyclosporin A (CsA) showed an anticancer effect on prostate cancer in cultured cell and xenograft models. E2F8 was identified as a master transcription factor that regulated a clinically significant CsA specific gene signature. The expression of E2F8 increased during prostate cancer progression and high levels of E2F8 expression are associated with a poor prognosis in patients with prostate cancer. MELK was identified as a crucial upstream regulator of E2F8 expression through the transcriptional regulatory network and Bayesian network analyses. Knockdown of E2F8 or MELK inhibited cell growth and colony formation in prostate cancer cells. High expression levels of E2F8 and androgen receptor (AR) are associated with a worse prognosis in patients with prostate cancer compared with low levels of both genes. The inhibition of E2F8 improved the response to AR blockade therapy. These results suggested that CsA has potential as an effective anticancer treatment for prostate cancer, while also revealing the oncogenic role of E2F8 and its association with clinical outcomes in prostate cancer. These results provided valuable insight into the development of therapeutic and diagnostic approaches for prostate cancer.
Asunto(s)
Neoplasias de la Próstata , Factores de Transcripción , Humanos , Masculino , Teorema de Bayes , Línea Celular Tumoral , Proliferación Celular , Ciclosporina/farmacología , Ciclosporina/uso terapéutico , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Proteínas Serina-Treonina Quinasas/genética , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Proteínas Represoras/genética , Factores de Transcripción/genéticaRESUMEN
BACKGROUND: Arterial cannulation in elderly patients is difficult because of age-related morphological changes. Applying dynamic needle tip positioning (DNTP) that guides the catheter to position inside the vessel sufficiently may aid in successful cannulation. METHODS: This prospective study enrolled patients aged over 70 years, who were scheduled for elective surgery under general anaesthesia with arterial cannulation. The patients were randomly assigned to the DNTP (group D, n = 76) or the conventional short-axis view(group C, n = 75) group. The arterial depth, diameter, and arterial conditions(calcification, segmental stenosis, and tortuosity) were evaluated using ultrasound, before puncture. We recorded the first attempt success, cannulation time, the number of attempts, and cannulation-related complications. RESULTS: A total of 151 patients were enrolled in this study. The first attempt success rate in group D was significantly higher than that in group C (89% versus 72%; P = 0.0168). The median cannulation time per last attempt in group D versus group C was 25 versus 30 sec(P = 0.0001), and the overall cannulation time was 25 versus 35 sec(P = 0.0001), respectively. Arterial cannulation per last attempt and overall cannulation time were shorter in group D. The number of attempts was higher in group C (P = 0.0038). The occurrence rate of hematoma was significantly lower in group D (16% versus 47%, relative risk = 3.0, P = 0.0001). CONCLUSIONS: The DNTP method may improve the first attempt success rate of arterial cannulation and reduce complications in elderly patients over 70 years of age.
Asunto(s)
Cateterismo Periférico , Arteria Radial , Anciano , Anciano de 80 o más Años , Humanos , Agujas , Estudios Prospectivos , Ultrasonografía IntervencionalRESUMEN
Crizotinib is a clinically approved tyrosine kinase inhibitor for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EML4-ALK fusion. Crizotinib was originally developed as an inhibitor of MET (HGF receptor), which is involved in the metastatic cascade. However, little is known about whether crizotinib inhibits tumor metastasis in NSCLC cells. In this study, we found that crizotinib suppressed TGFß signaling by blocking Smad phosphorylation in an ALK/MET/RON/ROS1-independent manner in NSCLC cells. Molecular docking and in vitro enzyme activity assays showed that crizotinib directly inhibited the kinase activity of TGFß receptor I through a competitive inhibition mode. Cell tracking, scratch wound, and transwell migration assays showed that crizotinib simultaneously inhibited TGFß- and HGF-mediated NSCLC cell migration and invasion. In addition, in vivo bioluminescence imaging analysis showed that crizotinib suppressed the metastatic capacity of NSCLC cells. Our results demonstrate that crizotinib attenuates cancer metastasis by inhibiting TGFß signaling in NSCLC cells. Therefore, our findings will help to advance our understanding of the anticancer action of crizotinib and provide insight into future clinical investigations.
Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Crizotinib/farmacología , Crizotinib/uso terapéutico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Simulación del Acoplamiento Molecular , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas , Pirazoles/farmacología , Pirazoles/uso terapéutico , Piridinas/farmacología , Piridinas/uso terapéutico , Factor de Crecimiento Transformador betaRESUMEN
BACKGROUND: Supraglottic airway (SGA) devices do not definitively protect the airway from regurgitation of gastric contents. Increased gastric pressure and long operation time are associated with development of complications such as aspiration pneumonia. The aim of this study was to compare intragastric pressure between second-generation SGA and endotracheal tube (ETT) devices during long-duration laparoscopic hepatectomy. METHODS: A total of 66 patients was randomly assigned to 2 groups; 33 patients each in the ETT and SGA groups. Intragastric pressure was continuously measured via a gastric drainage tube with a three-way stopcock connected to the pressure monitoring device. Normal saline was added to the end of the gastric drainage tube at each operation time point. RESULTS: Intragastric pressure during pneumoperitoneum was no different between the 2 groups (Pâ=â.146) or over time (Pâ=â.094). The mean (standard deviation [SD]) pH of the SGA tip measured after operation was 6.7 (0.4), and a pH <4 was not observed. Relative risk of postoperative complications was significantly higher in the ETT group relative to the SGA group (sore throat, 5.5; cough,13.0). CONCLUSIONS: Use of SGA devices does not further increase intragastric pressure, even during prolonged upper abdominal laparoscopic surgery. Also, the frequency of postoperative sore throat and cough was significantly lower when the second-generation SGA device was used.
Asunto(s)
Intubación Intratraqueal/instrumentación , Neumoperitoneo Artificial/efectos adversos , Complicaciones Posoperatorias/etiología , Presión/efectos adversos , Tos/etiología , Monitorización del pH Esofágico , Unión Esofagogástrica/fisiopatología , Unión Esofagogástrica/cirugía , Femenino , Hepatectomía/efectos adversos , Humanos , Laparoscopía/efectos adversos , Masculino , Persona de Mediana Edad , Tempo Operativo , Faringitis/etiología , Estudios Prospectivos , Estómago/fisiopatología , Estómago/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Pre-administration of remifentanil in target-controlled propofol and remifentanil anaesthesia could prolong the time of onset of muscle relaxation owing to haemodynamic effects, thereby prolonging the time to tracheal intubation. Although the sympatholytic effects of remifentanil result in bradycardia and hypotension, these responses can be attenuated by the administration of atropine. Therefore, we investigated whether prophylactic administration of atropine could prevent the prolongation of the time to tracheal intubation. METHODS: Sixty-four patients were included in this study. They were randomised into Group A (atropine 0.5 mg, n = 32) and Group S (saline 0.9%, n = 32), immediately before the pre-administration of remifentanil. The primary outcome was the time to tracheal intubation and the secondary outcomes were rocuronium onset time, time to loss of consciousness (LOC), time to reach a value of 60 on the bispectral index (BIS) and haemodynamic variables. RESULTS: The median [Interquartile range] of the time to tracheal intubation was 240 [214, 288]s in Group S and 190 [176, 212]s in Group A(median difference: 50 s, 95% confidence interval: 27-80 s, P = .001). Rocuronium onset time was significantly decreased in Group A compared to that in Group S (129 [110, 156] vs 172 [154, 200], P = .001). The times to LOC and reach 60 on the BIS were not significantly different between the two groups. Cardiac output(CO) and heart rate were less decreased in Group A than in Group S (P = .02, P < .001, respectively). CONCLUSIONS: Prophylactic administration of atropine could compensate for the reduction in CO in cases pre-administered with remifentanil in target-controlled propofol and remifentanil anaesthesia. This in turn prevented the prolongation of rocuronium onset time and reduced the time to tracheal intubation.
Asunto(s)
Atropina , Propofol , Anestésicos Intravenosos/farmacología , Presión Sanguínea , Frecuencia Cardíaca , Humanos , Intubación Intratraqueal , Piperidinas/farmacología , Propofol/farmacología , Remifentanilo/farmacologíaRESUMEN
OBJECTIVES: To evaluate the histologic effects of tamoxifen on the endometrium using hysteroscopy in postmenopausal women with breast cancer. METHODS: The study included 46 postmenopausal patients who were referred from another clinic due to thickening or bleeding of the endometrium after taking tamoxifen for breast cancer. All patients underwent transvaginal sonography (TVS) and hysteroscopic endometrial biopsy with a 5-mm, continuous-flow, operating hysteroscope. RESULTS: The incidence of malignancy was high (20%) in cases of abnormal uterine bleeding (AUB) after taking tamoxifen. However, in the non-AUB group with thick endometrium after taking tamoxifen, the incidence of adenocarcinoma was 3.2%. CONCLUSIONS: Our findings confirm the estrogen-like effect of tamoxifen on the endometrium. Endometrial evaluation with TVS suggests further diagnostic procedures; moreover, histologic examination is necessary under hysteroscopy, especially in cases of endometrial bleeding after taking tamoxifen.
RESUMEN
Expression of various molecules on the surface of cancer cells compared to normal cells creates a platform for the generation of various drug vehicles for targeted therapy. Multiple interactions between ligands and their receptors mediated by targeting peptide-modified polymer could enable simultaneous delivery of a drug selectively to target tumor cells, thus limiting side effects resulting from non-specific drug delivery. In this study, we synthesized a novel tumor targeting system by using two key elements: (1) Bld-1 peptide (SNRDARRC), a recently reported bladder tumor targeting peptide identified by using a phage-displayed peptide library, and (2) ELP, a thermally responsive polypeptide. B5V60 containing five Bld-1 peptides and non-targeted ELP77 with a thermal phase-transition over 37 °C were analyzed to determine their bioactivities. Further studies confirmed the superior binding ability of B5V60 to bladder tumor cells and the cellular accumulation of B5V60 in cancer cells was dependent on the expression level of sialyl-Tn antigen (STn), a tumor-associated carbohydrate antigen. Additionally, B5V60 displayed excellent localization in bladder tumor xenograft mice after intravenous injection and was strictly confined to sialyl-Tn antigen-overexpressing tumor tissue. Thus, our newly designed B5V60 showed high potential as a novel carrier for STn-specific targeted cancer therapy or other therapeutic applications.
Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Terapia Molecular Dirigida/métodos , Péptidos/farmacología , Secuencia de Aminoácidos/genética , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Elastina/metabolismo , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Péptidos/química , Péptidos/genética , Unión Proteica/fisiología , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
BACKGROUND: Early detection of tuberculosis (TB) is challenging in resource-poor settings because of limited accessibility to molecular diagnostics. The aim of this study was to evaluate the performance of the loop-mediated isothermal amplification kit (TB-LAMP) for TB diagnosis compared with conventional and molecular tests. METHODS: A total of 290 consecutive sputum samples were collected from May till September, 2015. All samples were processed using the N-Acetyl-L-cysteine (NALC) NaOH method and tested by smear microscopy, solid and liquid culture, real-time PCR, and TB-LAMP. RESULTS: The sensitivity of TB-LAMP for smear-positive and smear-negative samples with culture positivity was 92.0% and 58.8%, respectively. TB-LAMP was positive in 14.9% of TB culture-negative samples; however, all those samples were also positive by real-time PCR. In addition, none of the samples positive for nontuberculous mycobacteria by culture were positive by TB-LAMP. The overall agreement between TB-LAMP and real-time PCR was good; however, the concordance rate was significantly lower for real-time PCR positive samples with Ct values of 30-35. CONCLUSIONS: TB-LAMP could replace smear microscopy and increase TB diagnostic capacity when Xpert MTB/RIF is not feasible because of poor infrastructure.
Asunto(s)
Técnicas de Amplificación de Ácido Nucleico/métodos , Tuberculosis Pulmonar/diagnóstico , Técnicas de Cultivo , ADN Bacteriano/genética , ADN Bacteriano/metabolismo , Humanos , Mycobacterium/genética , Mycobacterium/aislamiento & purificación , Micobacterias no Tuberculosas/genética , Micobacterias no Tuberculosas/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad , Esputo/microbiología , Tuberculosis Pulmonar/microbiologíaRESUMEN
OBJECTIVES: To evaluate and compare the efficacy and safety of the combination of raloxifene and alendronate with those of monotherapies in elderly women with osteoporosis. METHODS: Sixty-two postmenopausal women (mean age 63.5 ± 0.5 years) attending gynecologic osteoporosis clinics with established osteoporosis were randomly allocated to one of four treatment groups and monitored for 3 years. All patients enrolled in this study, including those in the control group (n = 14), received 1.0 g elemental calcium and 400 units of vitamin D per day. The raloxifene group (n = 16) received raloxifene 60 mg (Evista®) per day; alendronate group (n = 17) received low-dose (5 mg) alendronate with calcitriol 0.5 µg (Maxmarvil®) per day; and the combination therapy group (n = 15) received both raloxifene 60 mg and low-dose (5 mg) alendronate with calcitriol 0.5 µg. Bone mineral density (BMD) was measured in the lumbar spine and hip before and after 3 years of treatment. RESULTS: In patients who received the combined therapy, BMD increased in the lumbar spine and the hip by 7.2% (P<0.001) and 4.8% (P<0.001) at 3 years. For patients in the alendronate group, the increases were 6.7% (P<0.001) and 3.1% (P<0.01) respectively, for the raloxifene group, the increases were 4.36% (P<0.001) and 1.9% (P<0.05) in the vertebrae and femora, respectively; however, the BMD of patients in the control group decreased by 1.81% (P<0.05) and 1.6% (P<0.05), respectively, after 3 years. Patients who received the combination therapy had significantly higher BMD in both the vertebrae femora (P<0.01) in comparison to that in those treated with raloxifene or alendronate individually. CONCLUSIONS: This 3-year randomized study showed the improved effects of alendronate and raloxifene combination on spine and hip BMD in elderly postmenopausal women with established osteoporosis.
RESUMEN
OBJECTIVES: We sought to describe the perioperative and postoperative adverse events associated with sacral colpopexy and evaluate the surgical outcome, complications, and benefits of laparoscopic sacral fixation for patients with pelvic prolapse. METHODS: Ninety-two women with uterine prolapse underwent sacral colpopexy between January 2011 and September 2016 at Chosun University Hospital. Patients' electronic medical records were investigated for demographic, intraoperative, and postoperative data. Strict definitions were used for all clinically relevant adverse events. Patients' outcomes were documented with 1 self-administered quality of life questionnaires: the Pelvic Floor Distress Inventory-20 focused on symptom distress. The primary analysis looking at perioperative and postoperative adverse events was descriptive and statistics were reported for all groups as n/N (%) with 95% confidence intervals for categorical variables and as mean ± standard deviation and mean (range) for all continuous variables. RESULTS: Their mean age was 69 ± 8.1 years, mean follow-up duration was 12 months, and mean operating time was 61 minutes. There were seven conversions due to anesthetic or surgical difficulties. Follow-up was performed using a telephone questionnaire and physical examination at 12 months. There were three cases of sacral pain with strong analgesics, one of vaginal erosion, two of transient urinary retentions, one of spondylitis, and two of mesh infection. Of the patients, 98.9% were satisfied with the surgical results, while none complained of sexual dysfunction or problems performing her usual activities. CONCLUSIONS: Laparoscopic sacral colpopexy is a feasible and highly effective technique that offers good long-term results with complication rates similar to those of open surgery with the added benefit of being minimally invasive.
RESUMEN
Western-style diet (WD) and dysbiosis are known to be associated with colonic inflammation, which contributes to carcinogenesis. Metformin (Met) exerts anti-inflammatory effects to induce AMP-activated protein kinase (AMPK), resulting in suppressed protein synthesis and reduced cell proliferation. Probiotic VSL#3 (V) modifies microbial composition. We investigated the chemopreventive mechanisms of Met and V in WD-induced colitis-associated colon carcinogenesis. Male BALB/c mice were randomly divided into five groups: a control diet (CD) group, WD group, WD+ Met (250mg/kg/day) group, WD+V (1.3 million bacteria/day) group, and WD+Met+V group. All mice were exposed to azoxymethane (10mg/kg) followed by 2% dextran sodium sulfate (DSS) for 7 days. Using HCT-116 human colon cancer cell line, expression of AMPK, extracellular signal-regulated kinase (ERK), cyclin D1, and Bcl-2 was investigated and cell cycle arrest was assessed. WD enhanced the severity of colitis and tumor growth compared with CD. The combination of Met and V significantly ameliorated colitis and tumor growth by inhibiting macrophage infiltration and maintaining epithelial integrity. In vitro assays showed that the combination therapy promoted late apoptosis by inhibiting cyclin D1 and Bcl-2 and activating pro-apoptotic ERK. A combination therapy with Met and V attenuates tumor growth in a mouse model of WD-induced colitic cancer, suggesting that this strategy could be useful for the chemoprevention of colon cancer.
Asunto(s)
Neoplasias del Colon/prevención & control , Dieta Occidental/efectos adversos , Metformina/farmacología , Probióticos/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Carcinogénesis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Colitis/complicaciones , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/complicaciones , Neoplasias del Colon/patología , Ciclina D1/antagonistas & inhibidores , Sinergismo Farmacológico , Activación Enzimática/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Masculino , RatonesRESUMEN
BACKGROUND AND AIM: Recent studies suggest that the anti-inflammatory agent balsalazide (BSZ) and probiotic agent VSL#3 have potential therapeutic benefits for the treatment of patients with inflammatory bowel disease. However, their effectiveness in preventing colitis-associated carcinogenesis (CAC) remains uncertain. The aim of the present study was to determine the chemopreventive effects of BSZ and VSL#3 in the murine azoxymethane (AOM)/dextran sodium sulfate (DSS) model. METHODS: C57B/L6J mice were randomly divided into four groups: CAC group, BSZ group, VSL#3 group, and BSZ + VSL#3 group. After 2 weeks, the AOM/DSS model was induced by AOM injection followed by two cycles of 2% DSS. RESULTS: During first and second cycles of DSS, the number of F4/80-positive macrophages was significantly lower in the drug-treated groups compared with the CAC group (P < 0.05). At the endpoint, the total numbers of tumors in the drug-treated groups were significantly low compared with the CAC group (P < 0.05), and the drug-treated groups had significantly lower F4/80-positive macrophages in the tumor stroma (P < 0.01). The protein production of macrophage inflammatory protein 1 beta, monocyte chemoattractant protein-1, interleukin (IL)-6, and IL-10 in the colon tissues decreased in concordance with the plasma concentrations of the cytokines (P < 0.05). The drug-treated groups revealed lower expression of p-STAT3 compared with the CAC group. In addition, BCL2 decreased, and BAX increased markedly in the BSZ + VSL#3 group. CONCLUSIONS: These results revealed that BSZ and VSL#3 have chemopreventive effects against CAC through IL-6/STAT3 suppression. BSZ and VSL#3 could be suitable options for chemoprevention of colorectal cancer.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Anticarcinógenos/farmacología , Transformación Celular Neoplásica/efectos de los fármacos , Colitis/tratamiento farmacológico , Colon/efectos de los fármacos , Neoplasias Colorrectales/prevención & control , Fármacos Gastrointestinales/farmacología , Interleucina-6/metabolismo , Mesalamina/farmacología , Fenilhidrazinas/farmacología , Probióticos/farmacología , Factor de Transcripción STAT3/metabolismo , Animales , Azoximetano , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/patología , Colon/metabolismo , Colon/patología , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Sulfato de Dextran , Modelos Animales de Enfermedad , Mediadores de Inflamación/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones Endogámicos C57BL , Fosforilación , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
BACKGROUND: Epicardial fat tissue is known to have an unique endocrine function which affect the cardiac autonomic system. Heart rate recovery (HRR) is a simple non-invasive measurement that assesses autonomic nervous system dysfunction. We aimed to investigate the association among epicardial fat thickness (EFT), HRR and circadian blood pressure (BP) variation in patients with hypertension. METHODS: A total of 358 consecutive patients who underwent both 24-hour ambulatory BP monitoring (ABPM) and a treadmill test were enrolled. Echocardiographic EFT and HRR, defined as peak heart rate minus heart rate after a 1-min recovery time, were measured. Patients were classified according to the ABPM; 147 patients with hypertension with a dipping pattern at night (dippers), 140 patients with hypertension with a non-dipping pattern at night (non-dippers) and 71 normotensive controls. RESULTS: EFT was significantly higher in hypertensive patients, especially in the non-dipper group, compared to the controls (non-dippers, 7.5 ± 2.9 mm; dippers, 6.6 ± 1.6 mm; controls, 5.5 ± 2.1 mm; p < 0.001). HRR was significantly lower in both hypertensive groups as compared to the control group and was the lowest in the non-dipper group (non-dipper, 26.6 ± 18.6; dipper, 29.5 ± 21.5; control, 71.4 ± 19.8; p < 0.001). EFT was significantly correlated with age, body mass index, 24-hour mean systolic BP and 24 h mean BP variability, whereas exercise duration, metabolic equivalents (METs) and HRR were inversely correlated with EFT. Furthermore, EFT > 6.7 mm was associated with a blunted HRR with 76 % sensitivity and 61 % specificity (ROC area under curve: 0.71, 95 % confidence interval, CI = 0.65-0.76, p < 0.001). In a multivariate analysis, EFT (odds ratio, OR = 3.53, 95 % CI = 1.20-10.37, p = 0.022) and 24-hour mean BP variability (OR = 1.09, 95 % CI = 1.03-1.16, p = 0.005) were independent predictors of a blunted HRR defined as HRR ≤ 12 beats (n = 63) in patients with hypertension. CONCLUSION: EFT and HRR were significantly correlated with circadian BP variability in patients with hypertension. EFT and circadian BP variability were independent predictors of blunted HRR, which suggests a link between epicardial fat and autonomic dysregulation in hypertension.
RESUMEN
OBJECTIVES: To access the effectiveness of radiofrequency myolysis (RFM) in women with midline dysmenorrhea. METHODS: We designed RFM in two ways laparoscopic RFM (LRFM), vaginal ultrasound-guided RFM (URFM). One hundred and thirty-two patients were in the LRFM group and, 140 patients were in the URFM group. RESULTS: Upon receipt of surgery, both the LRFM and the URFM groups demonstrated a significant decrease (P < 0.001) in the mean pain score when compared to those before and after surgery. CONCLUSION: The RF uterine myolysis procedure provides an alternative for those patients who suffer from intractable midline dysmenorrhea. LRFM is an alternative choice because it is relatively safe and, simple to perform and moreover, it is satisfactory. LRFM appears to increasingly succeed in the treatment of midline dysmenorrhea.
RESUMEN
Various human solid tumors highly express IL-4 receptors which amplify the expression of some of anti-apoptotic proteins, preventing drug-induced cancer cell death. Thus, IL-4 receptor targeted drug delivery can possibly increase the therapeutic efficacy in cancer treatment. Macromolecular carriers with multivalent targeting moieties offered great advantages in cancer therapy as they not only increase the plasma half-life of the drug but also allow delivery of therapeutic drugs to the cancer cells with higher specificity, minimizing the deleterious effects of the drug on normal cells. In this study we designed a library of elastin like polypeptide (ELP) polymers containing tumor targeting AP1 peptide using recursive directional ligation method. AP1 was previously discovered as an atherosclerotic plaque and breast tumor tissue homing peptide using phage display screening method, and it can selectively bind to the interleukin 4 receptor (IL-4R). The fluorescently labeled [AP1-V12]6, an ELP polymer containing six AP1 enhanced tumor-specific targeting ability and uptake efficiency in H226 and MDA-MB-231 cancer cell lines in vitro. Surface plasmon resonance analysis showed that multivalent presentation of the targeting ligand in the ELP polymer increased the binding affinity towards IL-4 receptor compared to free peptide. The binding of [AP1-V12]6 to cancer cells was remarkably reduced when IL-4 receptors were blocked by antibody against IL-4 receptor further confirmed its binding. Importantly, the Cy5.5-labeled [AP1-V12]6 demonstrated excellent homing and longer retention in tumor tissues in MDA-MB-231 xenograft mouse model. Immunohistological studies of tumor tissues further validated the targeting efficiency of [AP1-V12]6 to tumor tissue. These results indicate that designed [AP1-V12]6 can serve as a novel carrier for selective delivery of therapeutic drugs to tumors.
Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Elastina/farmacología , Subunidad alfa del Receptor de Interleucina-4/antagonistas & inhibidores , Proteínas de Neoplasias/antagonistas & inhibidores , Neoplasias/tratamiento farmacológico , Péptidos/farmacología , Animales , Línea Celular Tumoral , Elastina/genética , Humanos , Subunidad alfa del Receptor de Interleucina-4/genética , Subunidad alfa del Receptor de Interleucina-4/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Péptidos/genética , Resonancia por Plasmón de Superficie , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Hypoxia inducible factor 1α (HIF-1α), an essential transcriptional factor, is negatively regulated by two different types of oxygen and Fe(2+) -dependent HIF hydroxylases, proline hydroxylase (PHD) and factor inhibiting HIF (FIH), under normoxia. Iron chelators have therefore been used for inducing HIF-1α expression by inhibiting the hydroxylases. In this study, the iron chelators displayed differential effects for PHD and FIH in cells depending on their iron specificity and membrane permeability rather than their in vitro potencies. The membrane permeability of the strict Fe(2+) -chelator potentially inhibited both hydroxylases, whereas the membrane impermeable one showed no inhibitory effect in cells. In contrast, the depletion of the extracellular Fe(3+) ion was mainly correlated to PHD inhibition, and the membrane permeable one elicited low efficacy for both enzymes in cells. The 3'-hydroxyl group of quercetin, a natural flavonoid, was critical for inhibition of intracellular hydroxylases. Since the 3'-methylation of quercetin is induced by catechol-O-methyl transferase, the enzyme may regulate the intracellular activity of quercetin. These data suggest that the multiple factors of iron-chelators may be responsible for regulating the intracellular activity HIF hydroxylases.
Asunto(s)
Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Quelantes del Hierro/farmacología , Procolágeno-Prolina Dioxigenasa/metabolismo , Animales , Anticuerpos Monoclonales de Origen Murino/metabolismo , Permeabilidad de la Membrana Celular , Clonación Molecular , Activación Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Compuestos Férricos/metabolismo , Células HeLa , Humanos , Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/antagonistas & inhibidores , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Prolina Dioxigenasas del Factor Inducible por Hipoxia , Hierro/metabolismo , Ratones , Ratones Endogámicos BALB C , Oxigenasas de Función Mixta/genética , Oxigenasas de Función Mixta/metabolismo , Fenantrolinas/farmacología , Procolágeno-Prolina Dioxigenasa/antagonistas & inhibidores , Procolágeno-Prolina Dioxigenasa/genética , Unión Proteica , Quercetina/análogos & derivados , Quercetina/farmacología , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Transcripción GenéticaRESUMEN
PURPOSE: In this study, the effects of laughter therapy on levels of depression, quality of life, resilience and immune responses in breast cancer survivors were examined. METHODS: A quasi-experimental nonequivalent control group, pretest-posttest design was used. Participants (n=37) included breast cancer survivors who finished chemotheraphy and radiation therapy: 16 in the experiment group and 21 in the control group. Data were collected from August to November 2009. The experimental group participated in laughter therapy eight times, twice a week for 60 min per session. Questionnaires were used to measure pretest and posttest levels of depression, quality of life and resilience. A blood test was used to analyze changes in Total T cell, T helper, T suppressor, Th/Ts ratio, Total B cell, T cell/B cell ratio and NK cell for immune responses. RESULTS: The results showed that laughter therapy was effective in increasing the quality of life and resilience in breast cancer survivors. but depression and immune responses did not differ significantly between the groups. CONCLUSION: The results of the study indicate that laughter therapy may be an effective nursing intervention to improve quality of life and resilience in breast cancer survivors.
Asunto(s)
Neoplasias de la Mama/terapia , Depresión , Risoterapia , Calidad de Vida , Resiliencia Psicológica , Adulto , Anciano , Linfocitos B/inmunología , Linfocitos B/metabolismo , Neoplasias de la Mama/inmunología , Femenino , Humanos , Persona de Mediana Edad , Encuestas y Cuestionarios , Linfocitos T/inmunología , Linfocitos T/metabolismoRESUMEN
PURPOSE: The purpose of this study was to examine the effects of using gauze frozen with normal saline or ice on thirst-relief and oral condition of laparoscopic cholecystectomy patients. METHODS: A quasi-experimental nonequivalent control group, pretest-posttest design was used. Participants (n=53) received either gauze frozen with normal saline (n=17), ice (n=18) or wet gauze (n=18) for thirst-relief. The subjective thirst level and oral condition of the participants were assessed before the intervention, 15 min after the first intervention and 15 min after the second intervention. RESULTS: After oral care was provided twice, there were significant differences in thirst level among the groups. When oral care was provided twice, the oral condition of tongue, saliva, mucosal membrane, and gingiva was improved in patients receiving gauze frozen with normal saline or ice. CONCLUSION: Gauze frozen with normal saline and ice can be effective for oral care in reducing the thirst level and improving the condition of the oral cavity.
Asunto(s)
Colecistectomía Laparoscópica , Enfermedades de la Vesícula Biliar/cirugía , Hielo , Sed , Adulto , Anciano , Femenino , Congelación , Encía/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Mucosa Bucal/efectos de los fármacos , Proyectos Piloto , Solución Salina Hipertónica , Saliva/fisiología , Sed/efectos de los fármacos , Lengua/efectos de los fármacosRESUMEN
Recombinant adenovirus (Ad) has emerged as the vector system of choice in cancer gene therapy. Its full utility, however, has been limited because of the low efficiency of adenovirus-mediated gene transfer to cancer cells - the main reason being that cancer cells in general express inherently low levels of the coxsackie and adenovirus receptor (CAR) on their surface. Development of novel strategies to achieve adenovirus infection in a CAR-independent manner may help to overcome this limitation. To this end, we have generated a novel recombinant Ad, dl-VSVG-LacZ, that contains a fiber knob with intact CAR entry capability and an additional phosphatidylserine (PS) entry capability. This was achieved by incorporating the vesicular stomatitis virus glycoprotein (VSV-G) epitope onto the C terminus of the fiber knob. VSV-G is an envelope protein that facilitates the specificity for binding of the virus to PS moieties on the cellular plasma membrane. The newly tropism-expanded adenovirus, dl-VSVG-LacZ, showed a remarkable improvement (3- to 20-fold) in the delivery of LacZ to a variety of mammalian cells including those that were CAR deficient. The greatest improvement in gene transfer was observed in cells that were difficult to transduce with an untargeted Ad (wildtype fiber). Furthermore, treatment with dl-VSVG-LacZ significantly enhanced gene transfer in vivo when compared with control adenovirus that lacked the VSV-G epitope. Taken together, these studies demonstrate that the strategy to extend adenovirus tropism may greatly improve the utility of adenovirus in gene therapy applications.