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BACKGROUND: Skin quality may be assessed by degrees of skin smoothness, fine lines, and hydration. VYC-12L is a recently developed hyaluronic acid filler to improve skin quality. OBJECTIVE: This was a randomized, evaluator-blind study assessing safety and effectiveness of intradermal VYC-12L treatment for improving cheek skin smoothness, fine lines, and hydration. METHODS: Participants (≥22 years) with moderate-to-severe investigator-assessed Allergan Cheek Smoothness Scale (ACSS) scores were randomized in 2:1 ratio to receive VYC-12L or control (no treatment with optional treatment). Effectiveness was assessed 1 month after last injection (initial or touch-up) by a responder rate (≥1-grade improvement from baseline on both cheeks) using investigator-rated ACSS and Allergan Fine Lines Scale (AFLS), and tissue dielectric constant probe-measured skin hydration. Safety was evaluated throughout. RESULTS: Participants (VYC-12L, n = 131; control, n = 71) were 86.1% female with a median age of 58.0 years. At month 1, ACSS and AFLS responder rates were statistically significantly higher in the VYC-12L group (57.9%, 58.3%, respectively) than in the untreated controls (4.5%, 5.4%, respectively; p < .001). VYC-12L ACSS and AFLS responder rates remained consistent throughout the 6-month follow-up. Six participants reported treatment-related adverse events; none led to study discontinuation. CONCLUSION: VYC-12L is an effective, well-tolerated treatment for lasting improvement of cheek skin smoothness, fine lines, and hydration.
Assuntos
Técnicas Cosméticas , Preenchedores Dérmicos , Envelhecimento da Pele , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Técnicas Cosméticas/efeitos adversos , Melhoria de Qualidade , Satisfação do Paciente , Resultado do Tratamento , Ácido Hialurônico/efeitos adversosRESUMO
BACKGROUND: VYC-12L is a hyaluronic acid filler to improve skin quality. A prospective study showed safety and effectiveness of VYC-12L for improving cheek skin smoothness and fine lines. OBJECTIVES: To report participant-reported outcomes, subgroup analyses, and physician experience from the prospective study. METHODS: Adults with moderate to severe Allergan Cheek Skin Smoothness (ACSS) scale scores were randomized 2:1 to VYC-12L or control (no treatment with optional treatment). Participant assessments included FACE-Q Satisfaction With Skin, FACE-Q Appraisal of Lines, natural look and feel, the Global Aesthetic Improvement Scale (GAIS), and safety. Subgroup analyses examined ACSS responder rate (≥1-grade improvement from baseline to 1 month). RESULTS: FACE-Q Satisfaction With Skin overall mean scores improved from baseline to 1 month posttreatment by 32.0 and 1.4 in the VYC-12L and control groups, respectively. FACE-Q Appraisal of Lines overall mean scores improved from baseline to 1 month posttreatment by 23.3 and 0.4 in VYC-12L and control, respectively. Treated participants had high median scores (≥9.0) of natural look and feel of their cheek skin. GAIS responder rate was high at Month 1 (85.5%; 95% CI, 79.3%-91.7%) and through Month 6 (83.1%; 95% CI, 76.5%-89.7%). Mean participant-rated pain scores were low (<3). The most common injection site reactions were redness, swelling, and lumps/bumps; most resolved within 3 days. Subgroup analyses showed significant differences in ACSS responder rate between VYC-12L and control groups 1 month posttreatment. Physician injectors reported that VYC-12L was easily injected at the superficial skin and integrated quickly. CONCLUSIONS: VYC-12L treatment produced significant improvements in satisfaction with skin and cheek skin smoothness, as measured by participant-reported outcome measures.
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Técnicas Cosméticas , Preenchedores Dérmicos , Envelhecimento da Pele , Adulto , Humanos , Satisfação do Paciente , Bochecha , Estudos Prospectivos , Técnicas Cosméticas/efeitos adversos , Preenchedores Dérmicos/efeitos adversos , Ácido Hialurônico , Medidas de Resultados Relatados pelo Paciente , Resultado do TratamentoRESUMO
BACKGROUND: VYC-25L, a hyaluronic acid soft-tissue filler with lidocaine, is designed to restore and create facial volume in the chin and jaw. OBJECTIVE: To evaluate the safety and effectiveness of VYC-25L in subjects with chin retrusion. METHODS: Adults with chin retrusion (145°-165° glabella-subnasale-pogonion facial angle) were randomized (3:1) to receive VYC-25L in the chin/jaw at study onset (treatment group) or 3 months later (control group). Primary effectiveness end point was mean change in facial angle from baseline at Month 3. Safety assessments included injection site responses (ISRs), recorded in a subject diary, and adverse events (AEs). RESULTS: VYC-25L was administered to 119 subjects (treatment group: n = 90; control group: n = 29). Mean change in facial angle from baseline at Month 3 was significantly greater in the treatment versus control group (difference: 2.51°; p < .0001). Effectiveness was also demonstrated by the proportion of subjects with improved/much improved Global Aesthetic Improvement Scale scores and responses on FACE-Q Satisfaction and Psychological Well-Being Scales. Treatment benefit remained evident at Month 12. Common ISRs were firmness (95.8%), tenderness (95.8%), and swelling (91.6%). No serious treatment-related AEs were reported. CONCLUSION: VYC-25L significantly improved glabella-subnasale-pogonion facial angle and was generally safe and well tolerated.
Assuntos
Técnicas Cosméticas/efeitos adversos , Preenchedores Dérmicos/administração & dosagem , Ácido Hialurônico/administração & dosagem , Lidocaína/administração & dosagem , Envelhecimento da Pele/efeitos dos fármacos , Adulto , Idoso , Queixo , Preenchedores Dérmicos/efeitos adversos , Combinação de Medicamentos , Estética , Feminino , Humanos , Ácido Hialurônico/efeitos adversos , Reação no Local da Injeção/epidemiologia , Arcada Osseodentária , Lidocaína/efeitos adversos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: During the Pregnancy and Birth to 24 Months Project, the US Departments of Agriculture and Health and Human Services initiated a review of evidence on diet and health in these populations. OBJECTIVES: The aim of these systematic reviews was to examine the relation of 1) never versus ever feeding human milk, 2) shorter versus longer durations of any human milk feeding, 3) shorter versus longer durations of exclusive human milk feeding, and 4) feeding a lower versus higher intensity of human milk to mixed-fed infants with acute childhood leukemia, generally, and acute lymphoblastic leukemia, specifically. METHODS: The Nutrition Evidence Systematic Review team conducted systematic reviews with external experts. We searched CINAHL, Cochrane, Embase, and PubMed for articles published January 1980 to March 2016, dual-screened the results using predetermined criteria, extracted data from and assessed risk of bias for each included study, qualitatively synthesized the evidence, developed conclusion statements, and graded the strength of the evidence. RESULTS: We included 24 articles from case-control or retrospective studies. Limited evidence suggests that never feeding human milk versus 1) ever feeding human milk and 2) feeding human milk for durations ≥6 mo are associated with a slightly higher risk of acute childhood leukemia, whereas evidence comparing never feeding human milk with feeding human milk for durations <6 mo is mixed. Limited evidence suggests that, among infants fed human milk, a shorter versus longer duration of human milk feeding is associated with a slightly higher risk of acute childhood leukemia. None of the included articles examined exclusive human milk feeding or the intensity of human milk fed to mixed-fed infants. CONCLUSIONS: Feeding human milk for short durations or not at all may be associated with slightly higher acute childhood leukemia risk. The evidence could be strengthened with access to broadly generalizable prospective samples; therefore, we recommend linking surveillance systems that collect infant feeding and childhood cancer data.
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Dieta , Comportamento Alimentar , Fórmulas Infantis , Leucemia , Leite Humano , Aleitamento Materno , Criança , Saúde da Criança , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Leucemia/etiologia , Leucemia/prevenção & controle , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/prevenção & controleRESUMO
Natural products or nutraceuticals promote anti-aging, anti-cancer and other health-enhancing effects. A key target of the effects of natural products may be the regulation of the PI3K/PTEN/Akt/mTORC1/GSK-3 pathway. This review will focus on the effects of curcumin (CUR), berberine (BBR) and resveratrol (RES), on the PI3K/PTEN/Akt/mTORC1/GSK-3 pathway, with a special focus on GSK-3. These natural products may regulate the pathway by multiple mechanisms including: reactive oxygen species (ROS), cytokine receptors, mirco-RNAs (miRs) and many others. CUR is present the root of turmeric (Curcuma longa). CUR is used in the treatment of many disorders, especially in those involving inflammatory processes which may contribute to abnormal proliferation and promote cancer growth. BBR is also isolated from various plants (Berberis coptis and others) and is used in traditional medicine to treat multiple diseases/conditions including: diabetes, hyperlipidemia, cancer and bacterial infections. RES is present in red grapes, other fruits and berries such as blueberries and raspberries. RES may have some anti-diabetic and anti-cancer effects. Understanding the effects of these natural products on the PI3K/PTEN/Akt/mTORC1/GSK-3 pathway may enhance their usage as anti-proliferative agent which may be beneficial for many health problems.
Assuntos
Berberina/uso terapêutico , Curcumina/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/genética , Substâncias Protetoras/uso terapêutico , Estilbenos/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/enzimologia , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Quinase 3 da Glicogênio Sintase/metabolismo , Humanos , Inflamação , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Neoplasias/genética , Neoplasias/patologia , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/enzimologia , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , Osteoartrite/tratamento farmacológico , Osteoartrite/enzimologia , Osteoartrite/genética , Osteoartrite/patologia , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Resveratrol , Transdução de SinaisRESUMO
Natural products or nutraceuticals have been shown to elicit anti-aging, anti-cancer and other health-enhancing effects. A key target of the effects of natural products may be the regulation of microRNA (miR) expression which results in cell death or prevents aging, diabetes, cardiovascular and other diseases. This review will focus on a few natural products, especially on resveratrol (RES), curcumin (CUR) and berberine (BBR). RES is obtained from the skins of grapes and other fruits and berries. RES may extend human lifespan by activating the sirtuins and SIRT1 molecules. CUR is isolated from the root of turmeric (Curcuma longa). CUR is currently used in the treatment of many disorders, especially in those involving an inflammatory process. CUR and modified derivatives have been shown to have potent anti-cancer effects, especially on cancer stem cells (CSC). BBR is also isolated from various plants (e.g., Coptis chinensis) and has been used for centuries in traditional medicine to treat diseases such as adult- onset diabetes. Understanding the benefits of these and other nutraceuticals may result in approaches to improve human health.
Assuntos
Envelhecimento/efeitos dos fármacos , Suplementos Nutricionais , Neoplasias/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Linhagem Celular Tumoral , HumanosRESUMO
Chemotherapeutic drug treatment can result in the emergence of drug-resistant cells. By culturing an interleukin-3 (IL-3)-dependent cell line, FL5.12 cells in the presence of the chemotherapeutic drug doxorubicin, we isolated FL/Doxo cells which are multi-drug resistant. Increased levels of drug efflux were detected in FL/Doxo cells which could be inhibited by the MDR1 inhibitor verapamil but not by the MRP1 inhibitor MK571. The effects of TP53 and MEK1 were examined by infection of FL/Doxo cells with retroviruses encoding either a dominant negative TP-53 gene (FL/Doxo+ TP53 (DN) or a constitutively-activated MEK-1 gene (FL/Doxo + MEK1 (CA). Elevated MDR1 but not MRP1 mRNA transcripts were detected by quantitative RT-PCR in the drug-resistant cells while transcripts encoding anti-apoptotic genes such as: BCL2, BCLXL and MCL1 were observed at higher levels in the drug-sensitive FL5.12 cells. The percentage of cells that were side-population positive was increased in the drug-resistant cells compared to the parental line. Drug-resistance and side-positive population cells have been associated with cancer stem cells (CSC). Our studies suggest mechanisms which could allow the targeting of these molecules to prevent drug-resistance.
RESUMO
Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase that participates in an array of critical cellular processes. GSK-3 was first characterized as an enzyme that phosphorylated and inactivated glycogen synthase. However, subsequent studies have revealed that this moon-lighting protein is involved in numerous signaling pathways that regulate not only metabolism but also have roles in: apoptosis, cell cycle progression, cell renewal, differentiation, embryogenesis, migration, regulation of gene transcription, stem cell biology and survival. In this review, we will discuss the roles that GSK-3 plays in various diseases as well as how this pivotal kinase interacts with multiple signaling pathways such as: PI3K/PTEN/Akt/mTOR, Ras/Raf/MEK/ERK, Wnt/beta-catenin, hedgehog, Notch and TP53. Mutations that occur in these and other pathways can alter the effects that natural GSK-3 activity has on regulating these signaling circuits that can lead to cancer as well as other diseases. The novel roles that microRNAs play in regulation of the effects of GSK-3 will also be evaluated. Targeting GSK-3 and these other pathways may improve therapy and overcome therapeutic resistance.
Assuntos
Regulação Neoplásica da Expressão Gênica , Quinase 3 da Glicogênio Sintase/genética , MicroRNAs/genética , Mutação , Neoplasias/genética , Animais , Diferenciação Celular , Proliferação de Células , Sobrevivência Celular , Quinase 3 da Glicogênio Sintase/metabolismo , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , MicroRNAs/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Receptores Notch/genética , Receptores Notch/metabolismo , Transdução de Sinais , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , beta Catenina/genética , beta Catenina/metabolismoRESUMO
BACKGROUND: Banana is a staple food in many regions with high iron deficiency and may be a potential vehicle for iron fortification. However, iron absorption from bananas is not known. OBJECTIVE: The objective of this study was to evaluate total iron absorption from raw and cooked bananas. DESIGN: Thirty women (34.9±6.6 years) from rural Mexico were randomly assigned to one of two groups each consuming: 1) 480 g/day of raw banana for 6 days, or 2) 500 g/day of cooked banana for 4 days. Iron absorption was measured after extrinsically labeling with 2 mg of (58)Fe and a reference dose of 6 mg (57)Fe; analysis was done using ICP-MS. RESULTS: Iron content in cooked bananas was significantly higher than raw bananas (0.53 mg/100 g bananas vs. 0.33 mg/100 mg bananas, respectively) (p<0.001). Percent iron absorption was significantly higher in raw bananas (49.3±21.3%) compared with cooked banana (33.9±16.2%) (p=0.035). Total amount of iron absorbed from raw and cooked bananas was similar (0.77±0.33 mg vs. 0.86±0.41 mg, respectively). CONCLUSION: Total amount of absorbed iron is similar between cooked and raw bananas. The banana matrix does not affect iron absorption and is therefore a potential effective target for genetic modification for iron biofortification.
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The EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway plays prominent roles in malignant transformation, prevention of apoptosis, drug resistance and metastasis. The expression of this pathway is frequently altered in breast cancer due to mutations at or aberrant expression of: HER2, ERalpha, BRCA1, BRCA2, EGFR1, PIK3CA, PTEN, TP53, RB as well as other oncogenes and tumor suppressor genes. In some breast cancer cases, mutations at certain components of this pathway (e.g., PIK3CA) are associated with a better prognosis than breast cancers lacking these mutations. The expression of this pathway and upstream HER2 has been associated with breast cancer initiating cells (CICs) and in some cases resistance to treatment. The anti-diabetes drug metformin can suppress the growth of breast CICs and herceptin-resistant HER2+ cells. This review will discuss the importance of the EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway primarily in breast cancer but will also include relevant examples from other cancer types. The targeting of this pathway will be discussed as well as clinical trials with novel small molecule inhibitors. The targeting of the hormone receptor, HER2 and EGFR1 in breast cancer will be reviewed in association with suppression of the EGFR/PI3K/PTEN/Akt/mTORC1/GSK-3 pathway.
Assuntos
Neoplasias da Mama/genética , Receptores ErbB/genética , Complexos Multiproteicos/genética , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Serina-Treonina Quinases TOR/genética , Classe I de Fosfatidilinositol 3-Quinases , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina , Transdução de Sinais/genéticaRESUMO
The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) was initially identified and studied in the regulation of glycogen synthesis. GSK-3 functions in a wide range of cellular processes. Aberrant activity of GSK-3 has been implicated in many human pathologies including: bipolar depression, Alzheimer's disease, Parkinson's disease, cancer, non-insulin-dependent diabetes mellitus (NIDDM) and others. In some cases, suppression of GSK-3 activity by phosphorylation by Akt and other kinases has been associated with cancer progression. In these cases, GSK-3 has tumor suppressor functions. In other cases, GSK-3 has been associated with tumor progression by stabilizing components of the beta-catenin complex. In these situations, GSK-3 has oncogenic properties. While many inhibitors to GSK-3 have been developed, their use remains controversial because of the ambiguous role of GSK-3 in cancer development. In this review, we will focus on the diverse roles that GSK-3 plays in various human cancers, in particular in solid tumors. Recently, GSK-3 has also been implicated in the generation of cancer stem cells in various cell types. We will also discuss how this pivotal kinase interacts with multiple signaling pathways such as: PI3K/PTEN/Akt/mTORC1, Ras/Raf/MEK/ERK, Wnt/beta-catenin, Hedgehog, Notch and others.
Assuntos
Quinase 3 da Glicogênio Sintase/fisiologia , Neoplasias/enzimologia , Animais , Humanos , Neoplasias/genética , Neoplasias/fisiopatologiaRESUMO
BACKGROUND: Suction drains are commonly placed after rhytidectomy to avoid seroma formation that may result from dead spaces between skin layers. Fibrin sealants promote tissue adherence by crosslinking with extracellular matrix proteins, which may reduce the dead space under skin flaps. OBJECTIVES: The authors evaluate the safety and efficacy of the fibrin sealant (FS) VH S/D 4 s-apr (Artiss; Baxter Healthcare Corp, Deerfield, Illinois), added to standard-of-care (SoC) treatment, in improving flap adherence and reducing dead space in patients undergoing rhytidectomy. METHODS: Patients with planned facial rhytidectomy were enrolled in this phase 3, prospective, controlled, randomized, patient-blinded, multicenter trial. They received SoC treatment on 1 side of the face and adjunctive FS VH S/D 4 s-apr on the other. RESULTS: Seventy-five patients completed the trial. The mean (SD) drainage volume was 7.7 (7.4) mL from the sides treated with sealant and 20.0 (11.3) mL from the SoC-only sides (P < .0001). Rates of hematoma and seroma were similar for the 2 treatments, as were changes in postoperative skin sensitivity. Adverse events generally were mild; 2 serious adverse events were reported (wound abscess, dehydration). CONCLUSIONS: Adjunct use of FS VH S/D 4 s-apr in rhytidectomy was proven safe in this study. It significantly reduced drainage volumes without increasing the incidence of hematoma or seroma, which suggests that it eliminates dead space through improved flap adherence. LEVEL OF EVIDENCE: 2.
Assuntos
Adesivo Tecidual de Fibrina/uso terapêutico , Ritidoplastia/métodos , Retalhos Cirúrgicos/irrigação sanguínea , Cicatrização/efeitos dos fármacos , Adulto , Idoso , Drenagem/efeitos adversos , Drenagem/métodos , Feminino , Hematoma/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Ritidoplastia/efeitos adversos , Seroma/prevenção & controle , Método Simples-Cego , Envelhecimento da Pele/fisiologia , Resistência à Tração , Adesivos Teciduais/uso terapêutico , Cicatrização/fisiologiaRESUMO
BACKGROUND: Suction drains are commonly placed after rhytidectomy surgery to avoid seroma formation that may result from dead spaces between skin layers. Fibrin sealants promote tissue adherence by cross-linking with extracellular matrix proteins, which may reduce the dead space under skin flaps. OBJECTIVES: The authors evaluate the safety and preliminary efficacy of the fibrin sealant (FS) VH S/D 4 s-apr (ARTISS; Baxter Healthcare Corp, Deerfield, Illinois), added to standard-of-care (SoC) treatment, on tissue plane adherence and local hemostasis in rhytidectomy patients. METHODS: In this phase 2, prospective, controlled, randomized, evaluator- and patient-blinded, multicenter study, 45 patients (of 56 possible enrollees) received SoC treatment on 1 side of the face and adjunctive FS VH S/D 4 s-apr treatment on the other side. Outcomes measures included visual assessments of ecchymosis (by blinded reviewers), grading of ecchymosis and edema, drainage volumes, occurrence of hematoma/seroma, safety evaluations, and patient-reported assessments of pain, numbness, and treatment preferences postoperatively. RESULTS: Mean patient age was 55.1 years. Rates and grades of ecchymosis and edema were similar for the 2 treatments. The mean (SD) drainage volume 24 hours after surgery was 11.5 (13.7) mL from the FS VH S/D 4 s-apr-treated sides of the face and 26.8 (24.0) mL from the SoC-only sides (P < .0001). Patient assessments of pain, numbness, and preference favored treatment with FS VH S/D 4 s-apr. Adverse events were mild to moderate in severity. CONCLUSIONS: Adjuvant use of FS VH S/D 4 s-apr appears to be safe and results in lower drainage volumes than SoC treatment alone.
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Envelhecimento , Reagentes de Ligações Cruzadas/uso terapêutico , Adesivo Tecidual de Fibrina/uso terapêutico , Hemostáticos/uso terapêutico , Rejuvenescimento , Ritidoplastia/métodos , Envelhecimento da Pele , Adulto , Idoso , Reagentes de Ligações Cruzadas/efeitos adversos , Drenagem , Equimose/etiologia , Edema/etiologia , Dor Facial/etiologia , Feminino , Adesivo Tecidual de Fibrina/efeitos adversos , Hematoma/etiologia , Hemostáticos/efeitos adversos , Humanos , Hipestesia/etiologia , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/etiologia , Satisfação do Paciente , Estudos Prospectivos , Ritidoplastia/efeitos adversos , Ritidoplastia/normas , Seroma/etiologia , Padrão de Cuidado , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
Over the past 30 years, a relatively simple growth factor and its cognate receptor have provided seminal insights into the understanding of the genetic basis of cancer, as well as growth factor signalling. The epidermal growth factor (EGF), its cognate receptor (EGFR) and related family members have been shown to be important in normal, as well as the malignant growth of many cell types including: glioblastomata, astrocytomas, medulloblastomata, non-small cell lung carcinoma (NSCLC) and breast cancer. This review summarises the history of the EGFR gene and the v-ErbB oncogene, as well as diverse approaches developed to inhibit EGFR activity. The two most advanced therapies use either small-molecule cell membrane permeable kinase inhibitors or antibodies which prevent receptor activation. Recent clinical trials indicate that certain NSCLC patients have mutations in the EGFR gene which makes them more responsive to kinase inhibitors. These mutations appear to enhance the ability of the ligand to activate EGFR activity and also prolong the binding of the EGFR inhibitor to the kinase domain. Evidence to date suggests that these EGFR mutations in NSCLC occur more frequently in Japan than in the western hemisphere. Although these mutations are correlated with enhanced efficacy to the inhibitors in NSCLC, they can not explain or predict the sensitivity of many other cancer patients to the beneficial effects of the EGFR kinase inhibitors or antibody mediated therapy. As with as other small-molecule kinase inhibitors and susceptible diseases (e.g., imatinib and chronic myeloid leukaemia), resistance to EGFR inhibitors has been reported recently, documenting the requirement for development of multi-pronged therapeutic approaches. EGFR kinase inhibitors are also being evaluated as adjuvants in hormonal therapy of breast cancer - especially those which overexpress EGFR. Genetically engineered antibodies specific for the EGFR family member ErbB2 have been developed which show efficacy in the treatment of primary, and prevent the relapse of, breast cancer. Clearly, the EGF/EGFR signalling cascade has, and continues to play, an important role in the development of novel anticancer targeted therapies.
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Antineoplásicos/farmacologia , Fator de Crescimento Epidérmico/genética , Fator de Crescimento Epidérmico/metabolismo , Família Multigênica , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Farmacogenética , Antineoplásicos/uso terapêutico , Humanos , Neoplasias/genéticaRESUMO
BACKGROUND: One potentially sustainable approach to improving iron status at the community level is to encourage the consumption of local ascorbic acid-rich foods, in conjunction with meals high in nonheme iron. OBJECTIVE: The study, conducted in rural Mexico, measured stable isotopes of iron to evaluate the effect on iron absorption of the addition of 25 mg ascorbic acid as agua de limón (limeade) to 2 typical meals per day for 2 wk. DESIGN: Fifteen nonpregnant, nonlactating, iron-deficient (ferritin < 12 microg/L) women (x +/- SD age: 28.3 +/- 7.7 y) fasted overnight and were brought to a community clinic. After an initial blood sample, subjects consumed 0.25 mg (57)Fe with both breakfast and lunch for 14 d. On day 29, another blood sample was taken, and a reference dose of 2.7 mg (58)Fe with 25 mg ascorbic acid was given. For the following 15 d, participants consumed 0.25 mg (57)Fe added to both breakfast and lunch with 25 mg ascorbic acid added to each meal as limeade. A final blood sample was taken on day 59. RESULTS: Iron absorption was calculated from recovery of isotopes in blood obtained 14 d after administration of each isotope. When 25 mg ascorbic acid as limeade was added to test meals twice a day for 2 wk, iron absorption increased significantly (P < 0.001) in every subject: the mean absorption rose from 6.6 +/- 3.0% to 22.9 +/- 12.6%. CONCLUSIONS: The consumption of 25 mg ascorbic acid as limeade twice daily with meals substantially improved iron absorption and may improve the iron status of nonpregnant, nonlactating, iron-deficient women.