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1.
Eur J Cancer Care (Engl) ; 30(6): e13511, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34622502

RESUMEN

OBJECTIVE: This qualitative study was an integral part in the development of a multidisciplinary team-led school-based human papillomavirus vaccination health-promotion programme (MDL-SHPVP) aiming to increase HPV vaccine uptake in Hong Kong. Study findings will inform the design of the MDL-SHPVP by drawing on interview data regarding the expectations and needs of key stakeholders and potential programme users. METHODS: Eight mother-daughter dyads, four secondary school teachers, two school principals, three social workers and one school nurse were interviewed. All interviews were audio-recorded and transcribed verbatim for thematic analysis. RESULTS: Most participants had misconceptions about HPV and the vaccine. Alhough there was no immediate perceived need for the vaccination, most participants had favourable attitudes towards HPV inoculation and vaccines in general. Factors affecting vaccine uptake included perceptions about risk of infection, vaccine availability, and cost. Participants were largely open to suggested MDL-SHPVP components (videos, digital game, and group discussions). CONCLUSION: Findings have highlighted knowledge gaps among potential users and key stakeholders and will be used to inform the design of the MDL-SHPVP to ensure that their needs and expectations are addressed. Study findings may also aid future HPV vaccine promotion efforts and boost HPV vaccine uptake among youth in the city.


Asunto(s)
Alphapapillomavirus , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino , Adolescente , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Papillomaviridae , Infecciones por Papillomavirus/prevención & control , Aceptación de la Atención de Salud , Neoplasias del Cuello Uterino/prevención & control , Vacunación
2.
J Shoulder Elbow Surg ; 30(8): e493-e502, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33246080

RESUMEN

BACKGROUND: Because nerve injury of muscles around the shoulder can be easily disguised by "trick movements" of the trunk, shoulder dysfunction following brachial plexus injury is difficult to quantify with conventional clinical tools. Thus, to evaluate brachial plexus injury and quantify its biomechanical consequences, we used inertial measurement units, which offer the sensitivity required to measure the trunk's subtle movements. METHODS: We calculated 6 kinematic scores using inertial measurement units placed on the upper arms and the trunk during 9 functional tasks. We used both statistical and machine learning techniques to compare the bilateral asymmetry of the kinematic scores of 15 affected and 15 able-bodied individuals (controls). RESULTS: Asymmetry indexes from several kinematic scores of the upper arm and trunk showed a significant difference (P < .05) between the affected and control groups. A bagged ensemble of decision trees trained with trunk and upper arm kinematic scores correctly classified all controls. All but 2 patients were also correctly classified. Upper arm scores showed correlation coefficients ranging from 0.55-0.76 with conventional clinical scores. CONCLUSIONS: The proposed wearable technology is a sensitive and reliable tool for objective outcome evaluation of brachial plexus injury and its biomechanical consequences. It may be useful in clinical research and practice, especially in large cohorts with multiple follow-ups.


Asunto(s)
Neuropatías del Plexo Braquial , Plexo Braquial , Articulación del Hombro , Dispositivos Electrónicos Vestibles , Neuropatías del Plexo Braquial/diagnóstico , Humanos , Hombro
3.
BMC Pediatr ; 20(1): 445, 2020 09 23.
Artículo en Inglés | MEDLINE | ID: mdl-32967637

RESUMEN

BACKGROUND: Extravasation injury resulting from intravenous therapies delivered via peripheral intravenous catheters or umbilical and peripherally inserted central venous catheters is a common iatrogenic complication occurring in neonatal intensive care units. This study aimed to evaluate the effectiveness of an evidence-based clinical practice guideline in the prevention and management of neonatal extravasation injury by nurses. METHODS: A controlled before-and-after study was conducted in a neonatal unit. The clinical practice guideline was developed, and a multifaceted educational program was delivered to nurses. Neonatal outcomes, including the rates of peripheral intravenous extravasation and extravasation from a central line, were collected at the pre- and post-intervention periods. Post-intervention data for nurses, including the nurses' level of knowledge and adherence, were collected at six months after the program. RESULTS: 104 and 109 neonates were recruited in the pre-intervention period (control) and the post-intervention period (intervention), respectively. The extravasation rate before and after the intervention was 14.04 and 2.90 per 1,000 peripheral intravenous catheters days, respectively. The adjusted odds ratio of peripheral intravenous extravasation post-intervention compared with that of pre-intervention was 0.20 (95% confidence interval: 0.05-0.74; p = 0.02) after adjusting for peripheral intravenous catheter days. The extravasation from a central line rate of the control and intervention groups post-intervention was 4.94 and zero per 1,000 central venous catheter days, respectively. Fifty-nine registered nurses were recruited. At six months post-program, there were significant improvements in the nurses' level of knowledge and adherence. CONCLUSIONS: These findings suggest that the implementation of an evidence-based clinical practice guideline significantly reduced the rate of peripheral intravenous extravasation and extravasation from a central line in neonates. However, to maintain nurses' knowledge and adherence to the evidence-based practice, the educational program will have to be conducted periodically and incorporated into the nurses' induction program. TRIAL REGISTRATION: ClinicalTrials.gov, Identifiers: NCT04321447 . Registered 20 March 2020 - Retrospectively registered.


Asunto(s)
Cateterismo Periférico , Catéteres Venosos Centrales , Administración Intravenosa , Cateterismo Periférico/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Humanos , Recién Nacido , Infusiones Intravenosas , Unidades de Cuidado Intensivo Neonatal
4.
J Transl Med ; 14(1): 187, 2016 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-27342639

RESUMEN

BACKGROUND: Tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ) were originally identified to show potent anti-tumor activity and immunomodulatory capability. Unfortunately, several clinical studies of relevant cancer therapy did not observe significant response in maximum tolerated dose whether given alone or in combination. We have identified a tumor vasculature homing peptide (TCP-1 peptide) which targets only the vasculature of colorectal tumors but not normal blood vessels in animals and humans. In the current study, the antitumor effect of TCP-1/TNFα and TCP-1/IFNγ alone or in combination was studied in orthotopic colorectal tumor model. METHODS: TCP-1/TNFα and TCP-1/IFNγ recombinant proteins were prepared and i.v. injected to study the in vivo anticancer effect in orthotopic colorectal tumor model. Tumor apoptosis was determined by TUNEL staining and cleaved caspase-3 immunofluorescent staining. Tumor infiltrating lymphocytes were analyzed by immunofluorescent staining and flow cytometry. Western-blot was performed to examine the expression of proteins. Cell apoptosis was measured by Annexin V/PI flow cytometry. RESULTS: Targeted delivery of TNFα or IFNγ by TCP-1 peptide exhibited better antitumor activity than unconjugated format by inducing more tumor apoptosis and also enhancing antitumor immunity shown by increased infiltration of T lymphocytes inside the tumor. More importantly, combination therapy of TCP-1/TNFα and TCP-1/IFNγ synergistically suppressed tumor growth and alleviated systematic toxicity associated with untargeted therapy. This combination therapy induced massive apoptosis/secondary necrosis in the tumor. CONCLUSIONS: Taken together, our data demonstrate TCP-1 is an efficient drug carrier for targeted therapy of colorectal cancer (CRC). TCP-1/TNFα combined with TCP-1/IFNγ is a promising combination therapy for CRC.


Asunto(s)
Neoplasias Colorrectales/irrigación sanguínea , Neoplasias Colorrectales/patología , Interferón gamma/farmacología , Neovascularización Patológica/patología , Factor de Necrosis Tumoral alfa/farmacología , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/inmunología , Modelos Animales de Enfermedad , Interferón gamma/uso terapéutico , Ratones , Neovascularización Patológica/tratamiento farmacológico , Péptidos/farmacología , Factor de Necrosis Tumoral alfa/uso terapéutico
5.
Int J Nurs Stud ; 123: 104071, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34520886

RESUMEN

BACKGROUND: Misplacement of the nasogastric tube in the respiratory tract could cause serious complications and even death. Thus, nasogastric tube verification is necessary for optimal patient safety and comfort. Although end-tidal carbon dioxide detection is considered an effective approach to determine nasogastric tube location, there is a paucity of up-to-date evidence. OBJECTIVES: To review the diagnostic accuracy of end-tidal carbon dioxide detection in determining inadvertent airway intubation and verifying correct placement of nasogastric tubes. DESIGN: A systematic review and meta-analysis. METHODS: We searched clinical trials that evaluated the diagnostic accuracy of colorimetric capnometry or capnography in detecting nasogastric tubes located in the airway and differentiating between inadvertent airway intubation and correct nasogastric tube placement in any adult care setting. Four English language databases - Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and CINAHL - and four Chinese language databases - China Biomedical Literature Database, WanFang Data, China National Knowledge Infrastructure, and Airiti Library - were searched from July 2009 to March 2021. Clinical trial registration databases and reference lists of included studies and relevant reviews were also searched. Two reviewers extracted the data of all included studies using a data extraction form. Two reviewers assessed the methodological quality independently with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. We conducted meta-analysis using the hierarchical bivariate model and estimated the pool sensitivity and specificity of capnography and colorimetric capnometry. Forest plots were generated to display the results. Heterogeneity was investigated by meta-regression. The certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluations framework. RESULTS: Of 1,155 records identified, seven new studies were added to this update and a total of 16 studies were analysed in the systematic review. The total absolute number of true positive, false negative, true negative, and false positive observations were 142, 6, 1,500, and 65 respectively. Low to very low certainty of evidence indicated that the use of colorimetric capnometry or capnography is potentially an effective method in differentiating between respiratory and nasogastric tube placement for critically ill adult patients. Pooled results (13 studies, 1,541 intubations) for sensitivity and specificity were 0.96 (95% confidence interval [0.88, 0.99]) and 0.99 (95% confidence interval [0.96, 1.00]), respectively. CONCLUSIONS: Colorimetric capnometry and capnography may have the potential to be of high sensitivity and specificity for the detection of inadvertent airway nasogastric tube placements in critically ill adults. More evidence is required to generalize the updated findings to different types of patients and settings.


Asunto(s)
Dióxido de Carbono , Intubación Gastrointestinal , Adulto , Capnografía , Dióxido de Carbono/análisis , China , Humanos , Sensibilidad y Especificidad
6.
Nurse Educ Today ; 97: 104672, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33278729

RESUMEN

BACKGROUND: Extravasation injury remains a significant preventable cause of morbidity and mortality in neonates. Equipping nursing students with the requisite knowledge and skills is essential for appropriate prevention, early detection, and management of extravasation injury. OBJECTIVES: To develop a technology-enhanced, enquiry-based learning program for nursing students on the prevention and management of neonatal extravasation injury and examine its impact on their knowledge, approaches to studying and experience of learning. DESIGN: A pre-test/post-test study with qualitative evaluation. SETTINGS: Two university pre-registration nursing programs in Hong Kong. PARTICIPANTS: A total of 192 senior-year nursing students. METHODS: A novel learning program was developed comprising 25 scenario-based video vignettes supplemented with critical-thinking exercises, discussion guides, interactive games, reading materials and a 3-hour in-class interactive workshop. Students received unlimited online access to the program. Data were collected at baseline and one-month post-workshop. Outcomes were students' level of knowledge of prevention and management of extravasation injuries and related care, approaches to studying, and experience of learning. Paired t-tests were performed on pre- post-test outcome data and individual semi-structured interviews were conducted at one-month post-workshop, transcribed verbatim and analyzed thematically. RESULTS: There were statistically significant improvements in students' level of knowledge and use of a deep approach to learning at one month compared with baseline. Students were highly satisfied with the program, appreciating the video vignettes and interactive small group discussions with academics and clinicians. Suggestions for enhancing the program included more time for the workshop, interaction with clinicians, and details on the administration of neonatal medications and dosages. CONCLUSIONS: This study showed that a novel technology-enhanced, enquiry-based learning program was effective in enhancing nursing students' knowledge of the prevention and management of neonatal extravasation injury, approaches to studying and experience of learning.


Asunto(s)
Bachillerato en Enfermería , Estudiantes de Enfermería , Hong Kong , Humanos , Recién Nacido , Aprendizaje , Evaluación de Programas y Proyectos de Salud , Tecnología
7.
Medicine (Baltimore) ; 99(37): e22072, 2020 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-32925744

RESUMEN

INTRODUCTION: Evidence has consistently shown the high efficacy of human papillomavirus (HPV) vaccines in preventing cervical cancers. However, the HPV vaccine uptake rate in Hong Kong is very low. We will develop and evaluate an innovative, theory-based multidisciplinary team-led school-based HPV vaccination health-promotion program (MDL-SHPVP), engaging female adolescents, parents/guardians, and secondary school personnel in multicomponent educational strategies and interactive discussions. METHODS AND ANALYSIS: A cluster randomized controlled trial is proposed. We will recruit 2520 female adolescents and their parents/guardians from 18 secondary day schools. The MDL-SHPVP is underpinned by the Health Belief Model and Precaution Adoption Process Model. Multicomponent interventions will be offered, including education sessions with small group dialogues with a registered nurse and trained healthcare and lay volunteers, and educational computer games. A team of volunteers will be established to raise HPV, cervical cancer, and HPV vaccine awareness. Outcomes include adolescents' uptake of the HPV vaccine, adolescents' intention to receive HPV vaccination, vaccine acceptance among parents/guardians, and parents'/guardians' and adolescents' HPV knowledge, attitudes, and beliefs. Data will be collected at baseline, 1 month, and 1 year after intervention. The generalized estimating equations analysis will be used for comparing the outcomes between the 2 groups. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (Ref. no.: 2019.055). We will disseminate the study findings via peer-reviewed publications and presentations at relevant events and international and local conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT04438291.


Asunto(s)
Información de Salud al Consumidor/organización & administración , Vacunas contra Papillomavirus , Aceptación de la Atención de Salud , Servicios de Salud Escolar/organización & administración , Neoplasias del Cuello Uterino/prevención & control , Adolescente , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Padres/psicología , Factores Socioeconómicos , Estudiantes/psicología , Neoplasias del Cuello Uterino/virología
8.
Vascul Pharmacol ; 46(4): 271-7, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17188580

RESUMEN

In this study, we have investigated the actions of danshensu, an active, water-extractable component of the medicinal herb danshen (Salvia miltiorrhiza), on rat isolated coronary artery rings precontracted with 1 microM 5-hydroxytryptamine (5-HT) and its action compared to the water-extractable fraction of the herb. Extraction of the water-soluble fraction from danshen (S. miltiorrhiza) provided yield of 17.5% (35 g/200 g). The amount of danshensu determined in the crude danshen herb and in its aqueous fraction was 0.45 mg/g (0.045%) and 3.28 mg/g (0.33%). The danshen aqueous extract was 13 times less potent than danshensu in relaxing 5-HT-precontracted coronary artery rings; IC50 values were 930.3+/-133.5 microg/ml and 71.5+/-11.0 microg/ml. Removal of the endothelium did not significantly affect their vasodilator potencies; IC50 values were 842.1+/-123.8 microg/ml and 84.8+/-8.8 microg/ml. On the other hand, a potassium channel inhibitor tetraethylammonium (TEA, 10 mM) shifted their concentration-response curves by 1.7 and 2.2 folds. The possible involvement of Ca2+ channels was investigated in artery rings incubated with Ca2+-free buffer and primed with 1 microM 5-HT or 60 mM KCl for 5 min prior to addition of CaCl2 to elicit contraction. In 5-HT-primed preparations, the CaCl2-induced vasoconstriction was abolished by 2 mg/ml danshen aqueous extract and 200 microg/ml danshensu, whereas, in KCl-primed preparations, 10 mg/ml danshen aqueous extract and 600 microg/ml danshensu were required to abrogate the vasoconstriction. These findings suggest the vasorelaxant actions of danshen aqueous extract and danshensu were produced by inhibition of Ca2+ influx in the vascular smooth muscle cells. The opening of K+ channels had a minor contribution to the response, but endothelium-dependent mechanisms were not involved.


Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Lactatos/farmacología , Músculo Liso Vascular/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología , Animales , Calcio/metabolismo , Vasos Coronarios/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/química , Técnicas In Vitro , Lactatos/aislamiento & purificación , Masculino , Músculo Liso Vascular/metabolismo , Bloqueadores de los Canales de Potasio/farmacología , Canales de Potasio/metabolismo , Ratas , Ratas Sprague-Dawley , Salvia miltiorrhiza , Tetraetilamonio/farmacología
9.
Nutrients ; 9(5)2017 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-28531098

RESUMEN

There has been a dramatic rise in preterm births in developed countries owing to changes in clinical practices and greater use of assisted reproductive techniques. However, few studies have examined the growth and outcomes of preterm infants according to the type of feeding (with fortified breast milk or formula). The purpose of this study was to examine the effect of breast milk feedings and formula on the growth and short-term outcomes of preterm infants in Hong Kong. In a single-center retrospective cohort study, we included 642 preterm infants at gestational age <37 weeks with birth weights <2200 g. According to World Health Organization criteria, 466 were classified as low birth weight (LBW) infants (≥1500 g and <2200 g) and 176 were classified as very low birth weight (VLBW) infants (<1500 g). The mothers of approximately 80% of VLBW infants and 60% LBW infants initiated breast milk feeding. When compared with no breast milk intake, LBW infants that received breast milk were significantly more likely to have growth z-scores closer to the median of the reference population on admission and experienced slower weight gain from birth to discharge. When breast milk was categorized by percent of total enteral intake, significant differences were seen among LBW infants, with lower percentages of small-for-gestational-age (SGA) status at discharge with increased proportions of breast milk intake. Our results suggest that LBW infants fed breast milk had better growth z-scores and lower SGA status at discharge compared with those predominately fed preterm formula.


Asunto(s)
Fórmulas Infantiles , Recién Nacido de Bajo Peso/crecimiento & desarrollo , Leche Humana/química , Alimentos Fortificados , Humanos , Fenómenos Fisiológicos Nutricionales del Lactante , Recién Nacido , Recien Nacido Prematuro , Estudios Retrospectivos
10.
Artículo en Inglés | MEDLINE | ID: mdl-16737803

RESUMEN

This study investigates the pronounced synergism between the weak contractile action of prostaglandin E(2) (PGE(2)) and strong actions of phenylephrine, U-46619 and K(+) on rat isolated femoral artery. The potency ranking for synergism was SC-46275 (prostanoid receptor agonist selectivity: EP(3)>>EP(1))=sulprostone (EP(3)>EP(1))>17-phenyl PGE(2) (EP(1)>EP(3)). The novel EP(3) antagonist L-798106 (0.2-1microM) blocked the enhanced action of sulprostone (pA(2)=7.35-8.10), while the EP(1) antagonist SC-51322 (1microM) did not (pA(2)<6.0). Matching responses to priming agent and priming agent/sulprostone were similarly suppressed by nifedipine (300nM) and the selective Rho-kinase inhibitors H-1152 (0.1-1microM) and Y-27632 (1-10microM). Our findings implicate an EP(3) receptor in the prostanoid component of contractile synergism. While the synergism predominantly operates through a Ca(2+) influx-Rho-kinase pathway, the EP(3) receptor does not necessarily transduce via Rho-kinase.


Asunto(s)
Dinoprostona/farmacología , Arteria Femoral/efectos de los fármacos , Fenilefrina/farmacología , Potasio/farmacología , Vasoconstrictores/farmacología , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacología , Alprostadil/análogos & derivados , Alprostadil/farmacología , Animales , Dinoprostona/análogos & derivados , Dinoprostona/análisis , Interacciones Farmacológicas , Sinergismo Farmacológico , Técnicas In Vitro , Péptidos y Proteínas de Señalización Intracelular , Masculino , Nifedipino/farmacología , Prostaglandinas F Sintéticas/farmacología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Ratas , Ratas Sprague-Dawley , Receptores de Prostaglandina/agonistas , Receptores de Prostaglandina/metabolismo , Receptores de Prostaglandina E/agonistas , Receptores de Prostaglandina E/antagonistas & inhibidores , Receptores de Prostaglandina E/metabolismo , Subtipo EP1 de Receptores de Prostaglandina E , Subtipo EP3 de Receptores de Prostaglandina E , Sensibilidad y Especificidad , Sulfonamidas/metabolismo , Quinasas Asociadas a rho
11.
Eur J Emerg Med ; 23(4): 258-262, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25710083

RESUMEN

INTRODUCTION: Although there is consensus on the resuscitation of newborns, there is no standardization on how resuscitation equipment should be organized. This might lead to difficulty and inefficiency in retrieval of the right equipment during resuscitation. The neonatal resuscitation carts organized in accordance with the American Academy of Pediatrics (AAP) Neonatal Resuscitation Program (NRP) algorithm might result in more efficient retrieval of resuscitation equipment. OBJECTIVES: To compare user preference and lengths of time required to retrieve standard resuscitation equipment from an NRP Cart versus a generic storage drawer. STUDY DESIGN: A prospective, randomized, controlled, and crossover trial was conducted during simulation-based NRP provider courses in the Accident & Emergency Training Centre from September to October 2013. The mean time of accurate equipment retrieval and ease of use, which was rated by the participants using a five-point Likert scale (1=most difficult, 5=easiest to use), were compared using the Wilcoxon signed-rank test because of right skew. RESULTS: A total of 55 individuals participated in this study. The mean length of time required for equipment retrieval from the NRP Cart was significantly less than that from the drawer (Z=-3.90, P<0.01, median=36.23 s, interquartile range=97 s). In general, the NRP Cart was 32% faster than the drawer when extensive resuscitation equipment was required. All the participants rated the NRP Cart as easier to use than the drawer, with a median score of 4 for NRP Cart and 3 for the drawer (Z=-4.10, P<0.01, interquartile range=2). CONCLUSION: The NRP Cart was superior to the generic drawer in terms of the speed of equipment retrieval and user acceptability.


Asunto(s)
Resucitación/instrumentación , Algoritmos , Estudios Cruzados , Humanos , Recién Nacido , Estudios Prospectivos , Resucitación/métodos , Resucitación/normas , Factores de Tiempo
12.
J Control Release ; 210: 134-46, 2015 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-26003042

RESUMEN

Delivery and penetration of chemotherapeutic drugs into neoplasm through the tumor vasculature are essential mechanisms to enhance the efficiency of chemotherapy. "Vascular targeting" strategy focuses on promoting the infiltration of chemotherapeutic drugs into neoplastic tissues. In this study, we achieved a targeted therapy by coupling tumor necrosis factor α (TNFα) with TCP-1, a novel vascular-targeting peptide, in an orthotopic colorectal cancer model in mice. High dose of TCP-1-conjugated TNFα (TCP-1/TNFα: 5µg/mouse) displayed potent antitumor activity by inducing apoptosis and reducing microvessel number in tumors than unconjugated TNFα, with no evidence of increased toxicity. In the combined therapy, the antitumor action of 5-fluorouracil (5-FU) was potentiated when the mice were pretreated with a low dose of TNFα (1ng/mouse) and to a greater extent by the same concentration of TCP-1/TNFα. In this regard, TCP-1/TNFα combined with 5-FU synergistically inhibited the tumor growth, induced apoptosis and reduced cell proliferation. More importantly, TCP-1/TNFα normalized the tumor vasculature and facilitated the infiltration of immune cells to neoplasm as well as attenuated the immunosuppressing effects of TNFα in bone marrow and spleen. At the same time, TCP-1/TNFα significantly improved 5-FU absorption into the tumor mass. Taken together, these findings underscore the therapeutic potential of TCP-1 as a drug carrier in cancer therapy. TCP-1 is a novel vascular-targeting peptide and appears to be a promising agent for drug delivery. TCP-1 fused with TNFα holds great promise for colorectal cancer therapy.


Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Péptidos de Penetración Celular/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/administración & dosificación , Neovascularización Patológica/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/administración & dosificación , Animales , Antimetabolitos Antineoplásicos/química , Antimetabolitos Antineoplásicos/uso terapéutico , Médula Ósea/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Péptidos de Penetración Celular/química , Péptidos de Penetración Celular/uso terapéutico , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Fluorouracilo/química , Fluorouracilo/uso terapéutico , Proteínas Fluorescentes Verdes/administración & dosificación , Proteínas Fluorescentes Verdes/química , Humanos , Masculino , Ratones Endogámicos BALB C , Neovascularización Patológica/inmunología , Neovascularización Patológica/patología , Bazo/efectos de los fármacos , Carga Tumoral/efectos de los fármacos , Factor de Necrosis Tumoral alfa/química , Factor de Necrosis Tumoral alfa/inmunología , Factor de Necrosis Tumoral alfa/uso terapéutico
13.
Br J Pharmacol ; 160(6): 1352-61, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20590626

RESUMEN

BACKGROUND AND PURPOSE: Resveratrol, a naturally occurring polyphenolic antioxidant, has been shown to exhibit chemoprophylactic effects on cancer development. Previously, we reported that 2,3',4,4',5'-pentamethoxy-trans-stilbene (PMS), a methoxylated resveratrol derivative, exerted a highly potent anti-proliferative effect on human colon cancer cells as compared with its parent compound. In the present study, the chemopreventive effect of PMS was evaluated in a mouse model of colitis-associated colon carcinogenesis. EXPERIMENTAL APPROACH: Seven-week-old Balb/c mice were injected i.p. with 10 mg.kg(-1) azoxymethane (AOM). After 1 week, 3% dextran sodium sulphate (DSS) was administered in the drinking water for 7 days followed by 14 days of tap water for recovery, and this cycle was repeated twice. KEY RESULTS: Intragastric administration of PMS (25, 50 mg.kg(-1) body weight) for 16 weeks significantly reduced the multiplicity of colonic neoplasms by 15% and 35% (P < 0.01) respectively. Moreover, PMS at 50 mg.kg(-1) inhibited colon cancer cell proliferation and promoted apoptosis. Such changes were accompanied by reduction of Akt (protein kinase B) phosphorylation, inactivation of beta-catenin and down-regulation of inducible nitric oxide synthase. In parallel, in vitro studies also demonstrated that PMS inhibited proliferation and induced apoptosis in the murine colon adenocarcinoma cell line Colon26 with concomitant inhibition of Akt phosphorylation and inactivation of beta-catenin. CONCLUSIONS AND IMPLICATIONS: PMS effectively suppressed colon carcinogenesis in an AOM/DSS animal model and may merit further clinical investigation as a chemoprophylactic agent against colitis-associated colon cancer in humans.


Asunto(s)
Colitis/complicaciones , Neoplasias Colorrectales/prevención & control , Estilbenos/farmacología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Animales , Apoptosis/efectos de los fármacos , Azoximetano/toxicidad , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Ratones Endogámicos BALB C , Estilbenos/administración & dosificación
14.
J Control Release ; 148(3): 292-302, 2010 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-20854857

RESUMEN

Colorectal cancer (CRC) is the third most common malignancy and the fourth most frequent cause of cancer deaths worldwide. Ligand-mediated diagnosis and targeted therapy would have vital clinical applications in cancer treatment. In this study, an orthotopic model of colorectal cancer was established in mice. In vivo phage library selection was then utilized to isolate peptides specifically recognizing the vasculature of colorectal cancer tissues. A phage (termed TCP-1 phage) was isolated by this manner and it homed to the colorectal cancer tissues by 11- to 94-fold more than other organs. Chemical synthetic peptide (CTPSPFSHC, termed TCP-1) displayed by TCP-1 phage inhibited the homing ability of the phage to the tumor mass when co-injected intravenously with the TCP-1 phage into mice with colon cancer. Meanwhile, immunostaining analysis indicated that TCP-1 phage and peptide localized in the vasculature of the colorectal cancer tissue, but not of normal tissues. Moreover, TCP-1 peptide bound to blood vessels of surgical tissue samples of human colorectal cancer. After intravenous injection of FITC-labeled TCP-1 into the tumor-bearing mice for 20h, there was a strong fluorescent signal in the tumors but not other tissues when observed under blue light. In addition, TCP-1 conjugated with a pro-apoptotic peptide specifically induced apoptosis of tumor-associated blood vessels in vivo. The data define a novel peptide TCP-1 as an effective agent for imaging detection and drug delivery for colorectal cancer.


Asunto(s)
Neoplasias Colorrectales/irrigación sanguínea , Neoplasias Colorrectales/diagnóstico , Portadores de Fármacos/química , Biblioteca de Péptidos , Péptidos/química , Secuencia de Aminoácidos , Animales , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Portadores de Fármacos/síntesis química , Fluoresceína/administración & dosificación , Fluoresceína-5-Isotiocianato/química , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Microscopía Fluorescente , Péptidos/síntesis química
15.
J Cardiovasc Pharmacol ; 43(6): 795-807, 2004 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15167273

RESUMEN

This study investigates whether incomplete relaxation of vascular smooth muscle preparations induced by the prostacyclin analogue taprostene is due to partial agonism at prostanoid IP receptors. In the presence of the prostanoid EP4 receptor antagonist AH 23848, 3 microM taprostene induced 45% relaxation of phenylephrine-contracted guinea-pig saphenous vein rings and displaced log concentration-response curves for the prostacyclin analogues AFP-07, TEI-9063, and cicaprost to the right, parallel to their predicted addition curves. In contrast, taprostene interacted additively with prostaglandin E2 (PGE2), ONO-AE1-259 (selective EP2 agonist), and acetylcholine. Similarly, on rat tail artery contracted with phenylephrine, 3 microM taprostene (20% relaxation) opposed AFP-07- but not PGE2-induced relaxation. However, under U-46619-induced tone (AH 23848 absent), taprostene antagonized AFP-07 and cicaprost more than TEI-9063, suggesting that the latter has more than one relaxation mechanism. The presence of a sensitive EP3 contractile system in mouse aorta interfered with IP receptor-mediated relaxation. By generating tone with phenylephrine and the potent EP3 agonist sulprostone, it was possible to show that 3 microM taprostene (15% relaxation) selectively opposed relaxations induced by AFP-07, TEI-9063, and cicaprost. Our experiments indicate that taprostene is a partial agonist at prostanoid IP receptors, and may be a lead to an IP receptor antagonist.


Asunto(s)
Epoprostenol/análogos & derivados , Epoprostenol/farmacología , Músculo Liso Vascular/efectos de los fármacos , Receptores de Prostaglandina/agonistas , Animales , Relación Dosis-Respuesta a Droga , Epoprostenol/química , Cobayas , Técnicas In Vitro , Masculino , Ratones , Ratones Endogámicos BALB C , Músculo Liso Vascular/fisiología , Ratas , Ratas Sprague-Dawley , Receptores de Epoprostenol , Receptores de Prostaglandina/fisiología , Especificidad de la Especie , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiología
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